34 results on '"Sahar Esmaeeli"'
Search Results
2. Sleep apnoea is a risk factor for severe COVID-19
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Riitta Kaarteenaho, Nina Hautala, Athena Matakidou, Jaakko Kaprio, Ying Wu, Kai Kaarniranta, Peeter Karihtala, Kari Pulkki, Wei Zhou, Caroline Fox, Jussi Pihlajamäki, Apinya Lertratanakul, Juha Paloneva, Johannes Kettunen, Marita Kalaoja, Markus Perola, Veikko Salomaa, Hilkka Soininen, Mika Kähönen, Hao Chen, Andrey Loboda, Soumitra Ghosh, Anders Mälarstig, Markku Laakso, Marja Luodonpää, Markus Juonala, Xing Chen, Marika Crohns, Juhani Junttila, Sirkku Peltonen, Keith Usiskin, Juha Sinisalo, Aarno Palotie, Samuli Ripatti, Oili Kaipiainen-Seppänen, Aki Havulinna, Satu Strausz, Tuomo Kiiskinen, Martin Broberg, Sanni Ruotsalainen, Jukka Koskela, Tuula Palotie, Hanna M. Ollila, Mark Daly, Howard Jacob, Heiko Runz, Sally John, Robert Plenge, Mark McCarthy, Julie Hunkapiller, Meg Ehm, Dawn Waterworth, Kathy Klinger, Kathy Call, Tomi Mäkelä, Petri Virolainen, Terhi Kilpi, Jukka Partanen, Anne Pitkäranta, Seppo Vainio, Kimmo Savinainen, Veli-Matti Kosma, Urho Kujala, Outi Tuovila, Minna Hendolin, Raimo Pakkanen, Jeff Waring, States Bridget Riley-Gillis, Jimmy Liu, Shameek Biswas, Dorothee Diogo, Anders Pfizer, Catherine Marshall, Matthias Gossel, Johanna Schleutker, Mikko Arvas, Olli Carpen, Reetta Hinttala, Reijo Laaksonen, Arto Mannermaa, Valtteri Julkunen, Anne Remes, Reetta Kälviäinen, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha Rinne, Adam Ziemann, Jeffrey Waring, Sahar Esmaeeli, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, John Michon, Geoff Kerchner, Natalie Bowers, Edmond Teng, John Merck, Vinay Mehta, Padhraig Gormley, Kari Linden, Christopher Whelan, Fanli Xu, David Pulford, Martti Färkkilä, Sampsa Pikkarainen, Airi Jussila, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Bob Georgantas, Graham Heap, Fedik Rahimov, Joseph Maranville, Tim Lu, Danny Oh, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Johanna Huhtakangas, David Close, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Nina Mars, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Steven GreenbergCelgene, Hubert Chen, Jo Betts, Teemu Niiranen, Kaj Metsärinne, Marja-Riitta Taskinen, Tiinamaija Tuomi, Jari Laukkanen, Andrew Peterson Ben Challis, Audrey Chu, Jaakko Parkkinen, Anthony Muslin, Heikki Joensuu, Tuomo Meretoja, Lauri Aaltonen, Annika Auranen, Saila Kauppila, Päivi Auvinen, Klaus Elenius, Relja Popovic, Bridget Riley-Gillis, Jennifer Schutzman, Aparna Chhibber, Heli Lehtonen, Stefan McDonough, Diptee Kulkarni, Joni Turunen, Terhi Ollila, Sanna Seitsonen, Hannu Uusitalo, Vesa Aaltonen, Hannele Uusitalo-Järvinen, Erich Strauss, Anna Podgornaia, Joshua Hoffman, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Leena Koulu, Ilkka Harvima, David Choy, Anu Jalanko, Risto Kajanne, Ulrike Lyhs, Mari Kaunisto, Justin Davis, Danjuma Quarless, Slavé Petrovski, Chia-Yen Chen, Paola Bronson, Robert Yang, Diana Chang, Tushar Bhangale, Emily Holzinger, Xulong Wang, Åsa Hedman, Kirsi Auro, Clarence Wang, Ethan Xu, Franck Auge, Clement Chatelain, Mitja Kurki, Juha Karjalainen, Kimmo Palin, Priit Palta, Pietro Della, Susanna Lemmelä, Manuel Rivas, Jarmo Harju, Arto Lehisto, Andrea Ganna, Vincent Llorens, Antti Karlsson, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Tiina Wahlfors, Miika Koskinen, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Eija Laakkonen, Juha Kononen, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Hannele Mattsson, Tero Hiekkalinna, Manuel Jiménez, Kati Donner, Kalle Pärn, Javier Nunez-Fontarnau, Elina Kilpeläinen, Timo Sipilä, Georg Brein, Alexander Dada, Ghazal Awaisa, Anastasia Shcherban, Tuomas Sipilä, Hannele Laivuori, Harri Siirtola, Javier Tabuenca, Lila Kallio, Sirpa Soini, Kimmo Pitkänen, and Teijo Kuopio
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Medicine ,Diseases of the respiratory system ,RC705-779 - Abstract
Background Obstructive sleep apnoea (OSA) is associated with higher body mass index (BMI), diabetes, older age and male gender, which are all risk factors for severe COVID-19.We aimed to study if OSA is an independent risk factor for COVID-19 infection or for severe COVID-19.Methods OSA diagnosis and COVID-19 infection were extracted from the hospital discharge, causes of death and infectious diseases registries in individuals who participated in the FinnGen study (n=260 405). Severe COVID-19 was defined as COVID-19 requiring hospitalisation. Multivariate logistic regression model was used to examine association. Comorbidities for either COVID-19 or OSA were selected as covariates. We performed a meta-analysis with previous studies.Results We identified 445 individuals with COVID-19, and 38 (8.5%) of them with OSA of whom 19 out of 91 (20.9%) were hospitalised. OSA associated with COVID-19 hospitalisation independent from age, sex, BMI and comorbidities (p-unadjusted=5.13×10−5, OR-adjusted=2.93 (95% CI 1.02 to 8.39), p-adjusted=0.045). OSA was not associated with the risk of contracting COVID-19 (p=0.25). A meta-analysis of OSA and severe COVID-19 showed association across 15 835 COVID-19 positive controls, and n=1294 patients with OSA with severe COVID-19 (OR=2.37 (95% 1.14 to 4.95), p=0.021).Conclusion Risk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19.
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- 2021
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3. BOD1 Is Required for Cognitive Function in Humans and Drosophila.
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Sahar Esmaeeli-Nieh, Michaela Fenckova, Iain M Porter, M Mahdi Motazacker, Bonnie Nijhof, Anna Castells-Nobau, Zoltan Asztalos, Robert Weißmann, Farkhondeh Behjati, Andreas Tzschach, Ute Felbor, Harry Scherthan, Seyed Morteza Sayfati, H Hilger Ropers, Kimia Kahrizi, Hossein Najmabadi, Jason R Swedlow, Annette Schenck, and Andreas W Kuss
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Genetics ,QH426-470 - Abstract
Here we report a stop-mutation in the BOD1 (Biorientation Defective 1) gene, which co-segregates with intellectual disability in a large consanguineous family, where individuals that are homozygous for the mutation have no detectable BOD1 mRNA or protein. The BOD1 protein is required for proper chromosome segregation, regulating phosphorylation of PLK1 substrates by modulating Protein Phosphatase 2A (PP2A) activity during mitosis. We report that fibroblast cell lines derived from homozygous BOD1 mutation carriers show aberrant localisation of the cell cycle kinase PLK1 and its phosphatase PP2A at mitotic kinetochores. However, in contrast to the mitotic arrest observed in BOD1-siRNA treated HeLa cells, patient-derived cells progressed through mitosis with no apparent segregation defects but at an accelerated rate compared to controls. The relatively normal cell cycle progression observed in cultured cells is in line with the absence of gross structural brain abnormalities in the affected individuals. Moreover, we found that in normal adult brain tissues BOD1 expression is maintained at considerable levels, in contrast to PLK1 expression, and provide evidence for synaptic localization of Bod1 in murine neurons. These observations suggest that BOD1 plays a cell cycle-independent role in the nervous system. To address this possibility, we established two Drosophila models, where neuron-specific knockdown of BOD1 caused pronounced learning deficits and significant abnormalities in synapse morphology. Together our results reveal novel postmitotic functions of BOD1 as well as pathogenic mechanisms that strongly support a causative role of BOD1 deficiency in the aetiology of intellectual disability. Moreover, by demonstrating its requirement for cognitive function in humans and Drosophila we provide evidence for a conserved role of BOD1 in the development and maintenance of cognitive features.
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- 2016
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4. Both rare and de novo copy number variants are prevalent in agenesis of the corpus callosum but not in cerebellar hypoplasia or polymicrogyria.
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Samin A Sajan, Liliana Fernandez, Sahar Esmaeeli Nieh, Eric Rider, Polina Bukshpun, Mari Wakahiro, Susan L Christian, Jean-Baptiste Rivière, Christopher T Sullivan, Jyotsna Sudi, Michael J Herriges, Alexander R Paciorkowski, A James Barkovich, Joseph T Glessner, Kathleen J Millen, Hakon Hakonarson, William B Dobyns, and Elliott H Sherr
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Genetics ,QH426-470 - Abstract
Agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and polymicrogyria (PMG) are severe congenital brain malformations with largely undiscovered causes. We conducted a large-scale chromosomal copy number variation (CNV) discovery effort in 255 ACC, 220 CBLH, and 147 PMG patients, and 2,349 controls. Compared to controls, significantly more ACC, but unexpectedly not CBLH or PMG patients, had rare genic CNVs over one megabase (p = 1.48×10⁻³; odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.89-5.39). Rare genic CNVs were those that impacted at least one gene in less than 1% of the combined population of patients and controls. Compared to controls, significantly more ACC but not CBLH or PMG patients had rare CNVs impacting over 20 genes (p = 0.01; OR = 2.95; 95% CI = 1.69-5.18). Independent qPCR confirmation showed that 9.4% of ACC patients had de novo CNVs. These, in comparison to inherited CNVs, preferentially overlapped de novo CNVs previously observed in patients with autism spectrum disorders (p = 3.06×10⁻⁴; OR = 7.55; 95% CI = 2.40-23.72). Interestingly, numerous reports have shown a reduced corpus callosum area in autistic patients, and diminished social and executive function in many ACC patients. We also confirmed and refined previously known CNVs, including significantly narrowing the 8p23.1-p11.1 duplication present in 2% of our current ACC cohort. We found six novel CNVs, each in a single patient, that are likely deleterious: deletions of 1p31.3-p31.1, 1q31.2-q31.3, 5q23.1, and 15q11.2-q13.1; and duplications of 2q11.2-q13 and 11p14.3-p14.2. One ACC patient with microcephaly had a paternally inherited deletion of 16p13.11 that included NDE1. Exome sequencing identified a recessive maternally inherited nonsense mutation in the non-deleted allele of NDE1, revealing the complexity of ACC genetics. This is the first systematic study of CNVs in congenital brain malformations, and shows a much higher prevalence of large gene-rich CNVs in ACC than in CBLH and PMG.
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- 2013
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5. De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy
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Nieh, Sahar Esmaeeli, Madou, Maura RZ, Sirajuddin, Minhajuddin, Fregeau, Brieana, McKnight, Dianalee, Lexa, Katrina, Strober, Jonathan, Spaeth, Christine, Hallinan, Barbara E, Smaoui, Nizar, Pappas, John G, Burrow, Thomas A, McDonald, Marie T, Latibashvili, Mariam, Leshinsky-Silver, Esther, Lev, Dorit, Blumkin, Luba, Vale, Ronald D, Barkovich, Anthony James, and Sherr, Elliott H
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Biomedical and Clinical Sciences ,Neurosciences ,Genetics ,Neurodegenerative ,Pediatric ,Eye Disease and Disorders of Vision ,Rare Diseases ,Clinical Research ,Intellectual and Developmental Disabilities (IDD) ,Brain Disorders ,2.1 Biological and endogenous factors ,Neurological ,Clinical Sciences ,Clinical and health psychology - Abstract
ObjectiveTo determine the cause and course of a novel syndrome with progressive encephalopathy and brain atrophy in children.MethodsClinical whole-exome sequencing was performed for global developmental delay and intellectual disability; some patients also had spastic paraparesis and evidence of clinical regression. Six patients were identified with de novo missense mutations in the kinesin gene KIF1A. The predicted functional disruption of these mutations was assessed in silico to compare the calculated conformational flexibility and estimated efficiency of ATP binding to kinesin motor domains of wild-type (WT) versus mutant alleles. Additionally, an in vitro microtubule gliding assay was performed to assess the effects of de novo dominant, inherited recessive, and polymorphic variants on KIF1A motor function.ResultsAll six subjects had severe developmental delay, hypotonia, and varying degrees of hyperreflexia and spastic paraparesis. Microcephaly, cortical visual impairment, optic neuropathy, peripheral neuropathy, ataxia, epilepsy, and movement disorders were also observed. All six patients had a degenerative neurologic course with progressive cerebral and cerebellar atrophy seen on sequential magnetic resonance imaging scans. Computational modeling of mutant protein structures when compared to WT kinesin showed substantial differences in conformational flexibility and ATP-binding efficiency. The de novo KIF1A mutants were nonmotile in the microtubule gliding assay.InterpretationDe novo mutations in KIF1A cause a degenerative neurologic syndrome with brain atrophy. Computational and in vitro assays differentiate the severity of dominant de novo heterozygous versus inherited recessive KIF1A mutations. The profound effect de novo mutations have on axonal transport is likely related to the cause of progressive neurologic impairment in these patients.
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- 2015
6. New insights into the genetic etiology of Alzheimer's disease and related dementias
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Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. A., Piñol-Ripoll, G., Pisanu, C., Polak, T., Popp, J., Posthuma, D., Priller, J., Puerta, R., Quenez, O., Quintela, I., Thomassen, J. Q., Rábano, A., Rainero, I., Rajabli, F., Ramakers, I., Real, L. M., Reinders, M. J. T., Reitz, C., Reyes-Dumeyer, D., Ridge, P., Riedel-Heller, S., Riederer, P., Roberto, N., Rodriguez-Rodriguez, E., Rongve, A., Allende, I. R., Rosende-Roca, M., Royo, J. L., Rubino, E., Rujescu, D., Sáez, M. E., Sakka, P., Saltvedt, I., Sanabria, Á., Sánchez-Arjona, M. B., Sanchez-Garcia, F., Juan, P. S., Sánchez-Valle, R., Sando, S. B., Sarnowski, C., Satizabal, C. L., Scamosci, M., Scarmeas, N., Scarpini, E., Scheltens, P., Scherbaum, N., Scherer, M., Schmid, M., Schneider, A., Schott, J. M., Selbæk, G., Seripa, D., Serrano, M., Sha, J., Shadrin, A. A., Skrobot, O., Slifer, S., Snijders, G. J. L., Soininen, H., Solfrizzi, V., Solomon, A., Song, Y. E., Sorbi, S., Sotolongo-Grau, O., Spalletta, G., Spottke, A., Squassina, A., Stordal, E., Tartan, J. P., Tárraga, L., Tesí, N., Thalamuthu, A., Thomas, T., Tosto, G., Traykov, L., Tremolizzo, L., Tybjærg-Hansen, A., Uitterlinden, A., Ullgren, A., Ulstein, I., Valero, S., Valladares, O., Broeckhoven, C. V., Vance, J., Vardarajan, B. N., van der Lugt, A., Dongen, J. V., van Rooij, J., van Swieten, J., Vandenberghe, R., Verhey, F., Vidal, J. -S., Vogelgsang, J., Vyhnalek, M., Wagner, M., Wallon, D., Wang, L. -S., Wang, R., Weinhold, L., Wiltfang, J., Windle, G., Woods, B., Yannakoulia, M., Zare, H., Zhao, Y., Zhang, X., Zhu, C., Zulaica, M., Laczo, J., Matoska, V., Serpente, M., Assogna, F., Piras, F., Ciullo, V., Shofany, J., Ferrarese, C., Andreoni, S., Sala, G., Zoia, C. P., Zompo, M. D., Benussi, A., Bastiani, P., Takalo, M., Natunen, T., Laatikainen, T., Tuomilehto, J., Antikainen, R., Strandberg, T., Lindström, J., Peltonen, M., Abraham, R., Al-Chalabi, A., Bass, N. J., Brayne, C., Brown, K. S., Collinge, J., Craig, D., Deloukas, P., Fox, N., Gerrish, A., Gill, M., Gwilliam, R., Harold, D., Hollingworth, P., Johnston, J. A., Jones, L., Lawlor, B., Livingston, G., Lovestone, S., Lupton, M., Lynch, A., Mann, D., Mcguinness, B., Mcquillin, A., O’Donovan, M. C., Owen, M. J., Passmore, P., Powell, J. F., Proitsi, P., Rossor, M., Shaw, C. E., Smith, A. D., Gurling, H., Todd, S., Mummery, C., Ryan, N., Lacidogna, G., Adarmes-Gómez, A., Mauleón, A., Pancho, A., Gailhajenet, A., Lafuente, A., Macias-García, D., Martín, E., Pelejà, E., Carrillo, F., Merlín, I. S., Garrote-Espina, L., Vargas, L., Carrion-Claro, M., Marín, M., Labrador, M., Buendia, M., Alonso, M. D., Guitart, M., Moreno, M., Ibarria, M., Periñán, M., Aguilera, N., Gómez-Garre, P., Cañabate, P., Escuela, R., Pineda-Sánchez, R., Vigo-Ortega, R., Jesús, S., Preckler, S., Rodrigo-Herrero, S., Diego, S., Vacca, A., Roveta, F., Salvadori, N., Chipi, E., Boecker, H., Laske, C., Perneczky, R., Anastasiou, C., Janowitz, D., Malik, R., Anastasiou, A., Parveen, K., López-García, S., Antonell, A., Mihova, K. Y., Belezhanska, D., Weber, H., Kochen, S., Solis, P., Medel, N., Lisso, J., Sevillano, Z., Politis, D. G., Cores, V., Cuesta, C., Ortiz, C., Bacha, J. I., Rios, M., Saenz, A., Abalos, M. S., Kohler, E., Palacio, D. L., Etchepareborda, I., Kohler, M., Novack, G., Prestia, F. A., Galeano, P., Castaño, E. M., Germani, S., Toso, C. R., Rojo, M., Ingino, C., Mangone, C., Rubinsztein, D. C., Teipel, S., Fievet, N., Deramerourt, V., Forsell, C., Thonberg, H., Bjerke, M., Roeck, E. D., Martínez-Larrad, M. T., Olivar, N., Cano, A., Macias, J., Maroñas, O., Nuñez-Llaves, R., Olivé, C., Adarmes-Gómez, A. D., Amer-Ferrer, G., Antequera, M., Burguera, J. A., Casajeros, M. J., Martinez de Pancorbo, M., Hevilla, S., Espinosa, M. A. L., Legaz, A., Manzanares, S., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, V., Martínez-Lage Álvarez, P., Iriarte, M. M., Periñán-Tocino, M. T., Real de Asúa, D., Rodrigo, S., Sastre, I., Vicente, M. P., Vivancos, L., Epelbaum, J., Hannequin, D., Campion, D., Deramecourt, V., Tzourio, C., Brice, A., Dubois, B., Williams, A., Thomas, C., Davies, C., Nash, W., Dowzell, K., Morales, A. C., Bernardo-Harrington, M., Turton, J., Lord, J., Brown, K., Vardy, E., Fisher, E., Warren, J. D., Ryan, N. S., Guerreiro, R., Uphill, J., Bass, N., Heun, R., Kölsch, H., Schürmann, B., Lacour, A., Herold, C., Powell, J., Patel, Y., Hodges, A., Becker, T., Warden, D., Wilcock, G., Clarke, R., Ben-Shlomo, Y., Hooper, N. M., Pickering-Brown, S., Sussams, R., Warner, N., Bayer, A., Heuser, I., Drichel, D., Klopp, N., Mayhaus, M., Riemenschneider, M., Pinchler, S., Feulner, T., Gu, W., van den Bussche, H., Hüll, M., Frölich, L., Wichmann, H. -E., Jöckel, K. -H., O’Donovan, M., Owen, M., Bahrami, S., Bosnes, I., Selnes, P., Bergh, S., Palotie, A., Daly, M., Jacob, H., Matakidou, A., Runz, H., John, S., Plenge, R., Mccarthy, M., Hunkapiller, J., Ehm, M., Waterworth, D., Fox, C., Malarstig, A., Klinger, K., Call, K., Behrens, T., Loerch, P., Mäkelä, T., Kaprio, J., Virolainen, P., Pulkki, K., Kilpi, T., Perola, M., Partanen, J., Pitkäranta, A., Kaarteenaho, R., Vainio, S., Turpeinen, M., Serpi, R., Laitinen, T., Mäkelä, J., Kosma, V. -M., Kujala, U., Tuovila, O., Hendolin, M., Pakkanen, R., Waring, J., Riley-Gillis, B., Liu, J., Biswas, S., Diogo, D., Marshall, C., Hu, X., Gossel, M., Graham, R., Cummings, B., Ripatti, S., Schleutker, J., Arvas, M., Carpén, O., Hinttala, R., Kettunen, J., Mannermaa, A., Laukkanen, J., Julkunen, V., Remes, A., Kälviäinen, R., Peltola, J., Tienari, P., Rinne, J., Ziemann, A., Esmaeeli, S., Smaoui, N., Lehtonen, A., Eaton, S., Lahdenperä, S., van Adelsberg, J., Michon, J., Kerchner, G., Bowers, N., Teng, E., Eicher, J., Mehta, V., Gormley, P., Linden, K., Whelan, C., Xu, F., Pulford, D., Färkkilä, M., Pikkarainen, S., Jussila, A., Blomster, T., Kiviniemi, M., Voutilainen, M., Georgantas, B., Heap, G., Rahimov, F., Usiskin, K., Lu, T., Oh, D., Kalpala, K., Miller, M., Mccarthy, L., Eklund, K., Palomäki, A., Isomäki, P., Pirilä, L., Kaipiainen-Seppänen, O., Huhtakangas, J., Lertratanakul, A., Hochfeld, M., Bing, N., Gordillo, J. E., Mars, N., Pelkonen, M., Kauppi, P., Kankaanranta, H., Harju, T., Close, D., Greenberg, S., Chen, H., Betts, J., Ghosh, S., Salomaa, V., Niiranen, T., Juonala, M., Metsärinne, K., Kähönen, M., Junttila, J., Laakso, M., Pihlajamäki, J., Sinisalo, J., Taskinen, M. -R., Tuomi, T., Challis, B., Peterson, A., Chu, A., Parkkinen, J., Muslin, A., Joensuu, H., Meretoja, T., Aaltonen, L., Mattson, J., Auranen, A., Karihtala, P., Kauppila, S., Auvinen, P., Elenius, K., Popovic, R., Schutzman, J., Loboda, A., Chhibber, A., Lehtonen, H., Mcdonough, S., Crohns, M., Kulkarni, D., Kaarniranta, K., Turunen, J. A., Ollila, T., Seitsonen, S., Uusitalo, H., Aaltonen, V., Uusitalo-Järvinen, H., Luodonpää, M., Hautala, N., Loomis, S., Strauss, E., Podgornaia, A., Hoffman, J., Tasanen, K., Huilaja, L., Hannula-Jouppi, K., Salmi, T., Peltonen, S., Koulu, L., Harvima, I., Wu, Y., Choy, D., Pussinen, P., Salminen, A., Salo, T., Rice, D., Nieminen, P., Palotie, U., Siponen, M., Suominen, L., Mäntylä, P., Gursoy, U., Anttonen, V., Sipilä, K., Davis, J. W., Quarless, D., Petrovski, S., Wigmore, E., Chen, C. -Y., Bronson, P., Tsai, E., Huang, Y., Maranville, J., Shaikho, E., Mohammed, E., Wadhawan, S., Kvikstad, E., Caliskan, M., Chang, D., Bhangale, T., Pendergrass, S., Holzinger, E., Chen, X., Hedman, Å., King, K. S., Wang, C., Xu, E., Auge, F., Chatelain, C., Rajpal, D., Liu, D., Xia, T. -H., Brauer, M., Kurki, M., Karjalainen, J., Havulinna, A., Jalanko, A., Palta, P., della Briotta Parolo, P., Zhou, W., Lemmelä, S., Rivas, M., Harju, J., Lehisto, A., Ganna, A., Llorens, V., Laivuori, H., Rüeger, S., Niemi, M. E., Tukiainen, T., Reeve, M. P., Heyne, H., Palin, K., Garcia-Tabuenca, J., Siirtola, H., Kiiskinen, T., Lee, J., Tsuo, K., Elliott, A., Kristiansson, K., Hyvärinen, K., Ritari, J., Koskinen, M., Pylkäs, K., Kalaoja, M., Karjalainen, M., Mantere, T., Kangasniemi, E., Heikkinen, S., Laakkonen, E., Sipeky, C., Heron, S., Karlsson, A., Jambulingam, D., Rathinakannan, V. S., Kajanne, R., Aavikko, M., Jiménez, M. G., della Briotta Parola, P., Kanai, M., Kaunisto, M., Kilpeläinen, E., Sipilä, T. P., Brein, G., Awaisa, G., Shcherban, A., Donner, K., Loukola, A., Laiho, P., Sistonen, T., Kaiharju, E., Laukkanen, M., Järvensivu, E., Lähteenmäki, S., Männikkö, L., Wong, R., Mattsson, H., Hiekkalinna, T., Paajanen, T., Pärn, K., Gracia-Tabuenca, J., Abner, E., Adams, P. M., Aguirre, A., Albert, M. S., Albin, R. L., Allen, M., Alvarez, L., Apostolova, L. G., Arnold, S. E., Asthana, S., Atwood, C. S., Ayres, G., Baldwin, C. T., Barber, R. C., Barnes, L. L., Beach, T. G., Becker, J. T., Beecham, G. W., Beekly, D., Benitez, B. A., Bennett, D., Bertelson, J., Margaret, F. E., Bird, T. D., Blacker, D., Boeve, B. F., Bowen, J. D., Boxer, A., Brewer, J., Burke, J. R., Burns, J. M., Buxbaum, J. D., Cairns, N. J., Cao, C., Carlson, C. S., Carlsson, C. M., Carney, R. M., Carrasquillo, M. M., Chasse, S., Chesselet, M. -F., Chesi, A., Chin, N. A., Chui, H. C., Craft, S., Crane, P. K., Cribbs, D. H., Crocco, E. A., Cruchaga, C., Cullum, M., Darby, E., Davis, B., De Jager, P. L., Decarli, C., Detoledo, J., Dick, M., Dickson, D. W., Dombroski, B. A., Doody, R. S., Duara, R., Ertekin-Taner, N., Evans, D. A., Fairchild, T. J., Fallon, K. B., Farlow, M. R., Farrell, J. J., Fernandez-Hernandez, V., Ferris, S., Frosch, M. P., Galasko, D. R., Gamboa, A., Gearing, M., Geschwind, D. H., Ghetti, B., Gilbert, J. R., Grabowski, T. J., Graff-Radford, N. R., Grant, S. F. A., Green, R. C., Growdon, J. H., Hakonarson, H., Hall, J., Hamilton, R. L., Harari, O., Harrell, L. E., Haut, J., Head, E., Henderson, V. W., Hernandez, M., Hohman, T., Honig, L. S., Huebinger, R. M., Huentelman, M. J., Hulette, C. M., Hyman, B. T., Hynan, L. S., Ibanez, L., Jarvik, G. P., Jayadev, S., Jin, L. -W., Johnson, K., Johnson, L., Kamboh, M. I., Karydas, A. M., Katz, M. J., Kaye, J. A., Keene, C. D., Khaleeq, A., Kim, R., Knebl, J., Kowall, N. W., Kramer, J. H., Laferla, F. M., Lah, J. J., Larson, E. B., Lee, E. B., Lerner, A., Leung, Y. Y., Leverenz, J. B., Levey, A. I., Li, M., Lieberman, A. P., Lipton, R. B., Logue, M., Lyketsos, C. G., Malamon, J., Mains, D., Marson, D. C., Martiniuk, F., Mash, D. C., Masliah, E., Massman, P., Masurkar, A., Mccormick, W. C., Mccurry, S. M., Mcdavid, A. N., Mckee, A. C., Mesulam, M., Mez, J., Miller, B. L., Miller, C. A., Miller, J. W., Montine, T. J., Monuki, E. S., Morris, J. C., Myers, A. J., Nguyen, T., O’Bryant, S., Olichney, J. M., Ory, M., Palmer, R., Parisi, J. E., Paulson, H. L., Pavlik, V., Paydarfar, D., Perez, V., Peskind, E., Petersen, R. C., Phillips-Cremins, J. E., Pierce, A., Polk, M., Poon, W. W., Potter, H., Qu, L., Quiceno, M., Quinn, J. F., Raj, A., Raskind, M., Reiman, E. M., Reisberg, B., Reisch, J. S., Ringman, J. M., Roberson, E. D., Rodriguear, M., Rogaeva, E., Rosen, H. J., Rosenberg, R. N., Royall, D. R., Sager, M. A., Sano, M., Saykin, A. J., Schneider, J. A., Schneider, L. S., Seeley, W. W., Small, S., Smith, A. G., Smith, J. P., Sonnen, J. A., Spina, S., George-Hyslop, P. S., Stern, R. A., Stevens, A. B., Strittmatter, S. M., Sultzer, D., Swerdlow, R. H., Tanzi, R. E., Tilson, J. L., Trojanowski, J. Q., Troncoso, J. C., Tsuang, D. W., Van Deerlin, V. M., van Eldik, L. J., Vassar, R., Vinters, H. V., Vonsattel, J. -P., Weintraub, S., Welsh-Bohmer, K. A., Whitehead, P. L., Wijsman, E. M., Wilhelmsen, K. C., Williams, B., Williamson, J., Wilms, H., Wingo, T. S., Wisniewski, T., Woltjer, R. L., Woon, M., Wright, C. B., C. -K., Wu, Younkin, S. G., C. -E., Yu, Yu, L., Zhang, Y., Zhu, X., Adams, H., Akinyemi, R. O., Ali, M., Armstrong, N., Aparicio, H. J., Bahadori, M., Breteler, M., Chasman, D., Chauhan, G., Comic, H., Cox, S., Cupples, A. L., Davies, G., Decarli, C. S., Duperron, M. -G., Dupuis, J., Evans, T., Fan, F., Fitzpatrick, A., Fohner, A. E., Ganguli, M., Geerlings, M., Glatt, S. J., Gonzalez, H. M., Goss, M., Grabe, H., Habes, M., Heckbert, S. R., Hofer, E., Hong, E., Hughes, T., Kautz, T. F., Knol, M., Kremen, W., Lacaze, P., Lahti, J., Grand, Q. L., Litkowski, E., Li, S., Liu, X., Loitfelder, M., Manning, A., Maillard, P., Marioni, R., Mazoyer, B., van Lent, D. M., Mei, H., Mishra, A., Nyquist, P., O’Connell, J., Paus, T., Pausova, Z., Raikkonen-Talvitie, K., Riaz, M., Rich, S., Rotter, J., Romero, J., Roshchupkin, G., Saba, Y., Sargurupremraj, M., Schmidt, H., Schmidt, R., Shulman, J. M., Smith, J., Sekhar, H., Rajula, R., Shin, J., Simino, J., Sliz, E., Teumer, A., Thomas, A., Tin, A., Tucker-Drob, E., Vojinovic, D., Wang, Y., Weinstein, G., Williams, D., Wittfeld, K., Yanek, L., Yang, Y., Farrer, L. A., Psaty, B. M., Ghanbari, M., Raj, T., Sachdev, P., Mather, K., Jessen, F., Ikram, M. A., de Mendonça, A., Hort, J., Tsolaki, M., Pericak-Vance, M. A., Amouyel, P., Williams, J., Frikke-Schmidt, R., Clarimon, J., Deleuze, J. -F., Rossi, G., Seshadri, S., Andreassen, O. A., Ingelsson, M., Hiltunen, M., Sleegers, K., Schellenberg, G. D., van Duijn, C. M., Sims, R., van der Flier, W. M., Ruiz, A., Ramirez, A., Lambert J., -C, Jan, Laczo, Vaclav, Matoska, Maria, Serpente, Francesca, Assogna, Fabrizio, Piras, Federica, Piras, Valentina, Ciullo, Jacob, Shofany, Carlo, Ferrarese, Simona, Andreoni, Gessica, Sala, Chiara Paola Zoia, Maria Del Zompo, Benussi, Alberto, Patrizia, Bastiani, Mari, Takalo, Teemu, Natunen, Tiina, Laatikainen, Jaakko, Tuomilehto, Riitta, Antikainen, Timo, Strandberg, Jaana, Lindström, Markku, Peltonen, Richard, Abraham, Ammar, Al-Chalabi, Nicholas, J Bass, Carol, Brayne, Kristelle, S Brown, John, Collinge, David, Craig, Pangiotis, Deloukas, Nick, Fox, Amy, Gerrish, Michael, Gill, Rhian, Gwilliam, Denise, Harold, Paul, Hollingworth, Jarret, A Johnston, Lesley, Jones, Brian, Lawlor, Gill, Livingston, Simon, Lovestone, Michelle, Lupton, Aoibhinn, Lynch, David, Mann, Bernadette, Mcguinness, Andrew, Mcquillin, Michael, C O'Donovan, Michael, J Owen, Peter, Passmore, John, F Powell, Petra, Proitsi, Martin, Rossor, Christopher, E Shaw, A David Smith, Hugh, Gurling, Stephen, Todd, Catherine, Mummery, Nathalie, Ryan, Giordano, Lacidogna, Adarmes-Gómez, Ad, Ana, Mauleón, Ana, Pancho, Anna, Gailhajenet, Asunción, Lafuente, Macias-García, D, Elvira, Martín, Esther, Pelejà, Carrillo, F, Isabel Sastre Merlín, Garrote-Espina, L, Liliana, Vargas, Carrion-Claro, M, Marín, M, Labrador, Ma, Mar, Buendia, María Dolores Alonso, Marina, Guitart, Mariona, Moreno, Marta, Ibarria, Periñán, Mt, Nuria, Aguilera, Gómez-Garre, P, Pilar, Cañabate, Escuela, R, Pineda-Sánchez, R, Vigo-Ortega, R, Jesús, S, Silvia, Preckler, Silvia, Rodrigo-Herrero, Susana, Diego, Alessandro, Vacca, Fausto, Roveta, Nicola, Salvadori, Elena, Chipi, Henning, Boecker, Christoph, Laske, Robert, Perneczky, Costas, Anastasiou, Daniel, Janowitz, Rainer, Malik, Anna, Anastasiou, Kayenat, Parveen, Carmen, Lage, Sara, López-García, Anna, Antonell, Kalina Yonkova Mihova, Diyana, Belezhanska, Heike, Weber, Silvia, Kochen, Patricia, Solis, Nancy, Medel, Julieta, Lisso, Zulma, Sevillano, Daniel, G Politis, Valeria, Cores, Carolina, Cuesta, Cecilia, Ortiz, Juan Ignacio Bacha, Mario, Rios, Aldo, Saenz, Mariana Sanchez Abalos, Eduardo, Kohler, Dana Lis Palacio, Ignacio, Etchepareborda, Matias, Kohler, Gisela, Novack, Federico Ariel Prestia, Pablo, Galeano, Eduardo, M Castaño, Sandra, Germani, Carlos Reyes Toso, Matias, Rojo, Carlos, Ingino, Carlos, Mangone, David, C Rubinsztein, Stefan, Teipel, Nathalie, Fievet, Vincent, Deramerourt, Charlotte, Forsell, Håkan, Thonberg, Maria, Bjerke, Ellen De Roeck, María Teresa Martínez-Larrad, Natividad, Olivar, Amanda, Cano, Juan, Macias, Olalla, Maroñas, Raúl, Nuñez-Llaves, Clàudia, Olivé, Ester, Pelejá, Astrid, D Adarmes-Gómez, Guillermo, Amer-Ferrer, Martirio, Antequera, Juan Andrés Burguera, Fátima, Carrillo, Mario, Carrión-Claro, María José Casajeros, Marian Martinez de Pancorbo, Rocío, Escuela, Lorena, Garrote-Espina, Pilar, Gómez-Garre, Saray, Hevilla, Silvia, Jesús, Miguel Angel Labrador Espinosa, Agustina, Legaz, Daniel, Macias-García, Salvadora, Manzanares, Marta, Marín, Juan, Marín-Muñoz, Tamara, Marín, Begoña, Martínez, Victoriana, Martínez, Pablo Martínez-Lage Álvarez, Maite Mendioroz Iriarte, María Teresa Periñán-Tocino, Rocío, Pineda-Sánchez, Diego Real de Asúa, Silvia, Rodrigo, Isabel, Sastre, Maria Pilar Vicente, Rosario, Vigo-Ortega, Liliana, Vivancos, Jacques, Epelbaum, Didier, Hannequin, Dominique, Campion, Vincent, Deramecourt, Christophe, Tzourio, Alexis, Brice, Bruno, Dubois, Amy, Williams, Charlene, Thomas, Chloe, Davies, William, Nash, Kimberley, Dowzell, Atahualpa Castillo Morales, Mateus, Bernardo-Harrington, James, Turton, Jenny, Lord, Kristelle, Brown, Emma, Vardy, Elizabeth, Fisher, Jason, D Warren, Natalie, S Ryan, Rita, Guerreiro, James, Uphill, Nick, Bass, Reinhard, Heun, Heike, Kölsch, Britta, Schürmann, André, Lacour, Christine, Herold, Janet, A Johnston, John, Powell, Yogen, Patel, Angela, Hodges, Tim, Becker, Donald, Warden, Gordon, Wilcock, Robert, Clarke, Panagiotis, Deloukas, Yoav, Ben-Shlomo, Nigel, M Hooper, Stuart, Pickering-Brown, Rebecca, Sussams, Nick, Warner, Anthony, Bayer, Isabella, Heuser, Dmitriy, Drichel, Norman, Klopp, Manuel, Mayhaus, Matthias, Riemenschneider, Sabrina, Pinchler, Thomas, Feulner, Wei, Gu, Hendrik van den Bussche, Michael, Hüll, Lutz, Frölich, H-Erich, Wichmann, Karl-Heinz, Jöckel, Michael, O'Donovan, Michael, Owen, Shahram, Bahrami, Ingunn, Bosnes, Per, Selnes, Sverre, Bergh, Aarno, Palotie, Mark, Daly, Howard, Jacob, Athena, Matakidou, Heiko, Runz, Sally, John, Robert, Plenge, Mark, Mccarthy, Julie, Hunkapiller, Meg, Ehm, Dawn, Waterworth, Caroline, Fox, Anders, Malarstig, Kathy, Klinger, Kathy, Call, Tim, Behrens, Patrick, Loerch, Tomi, Mäkelä, Jaakko, Kaprio, Petri, Virolainen, Kari, Pulkki, Terhi, Kilpi, Markus, Perola, Jukka, Partanen, Anne, Pitkäranta, Riitta, Kaarteenaho, Seppo, Vainio, Miia, Turpeinen, Raisa, Serpi, Tarja, Laitinen, Johanna, Mäkelä, Veli-Matti, Kosma, Urho, Kujala, Outi, Tuovila, Minna, Hendolin, Raimo, Pakkanen, Jeff, Waring, Bridget, Riley-Gillis, Jimmy, Liu, Shameek, Biswas, Dorothee, Diogo, Catherine, Marshall, Xinli, Hu, Matthias, Gossel, Robert, Graham, Beryl, Cummings, Samuli, Ripatti, Johanna, Schleutker, Mikko, Arvas, Olli, Carpén, Reetta, Hinttala, Johannes, Kettunen, Arto, Mannermaa, Jari, Laukkanen, Valtteri, Julkunen, Anne, Remes, Reetta, Kälviäinen, Jukka, Peltola, Pentti, Tienari, Juha, Rinne, Adam, Ziemann, Jeffrey, Waring, Sahar, Esmaeeli, Nizar, Smaoui, Anne, Lehtonen, Susan, Eaton, Sanni, Lahdenperä, Janet van Adelsberg, John, Michon, Geoff, Kerchner, Natalie, Bowers, Edmond, Teng, John, Eicher, Vinay, Mehta, Padhraig, Gormley, Kari, Linden, Christopher, Whelan, Fanli, Xu, David, Pulford, Martti, Färkkilä, Sampsa, Pikkarainen, Airi, Jussila, Timo, Blomster, Mikko, Kiviniemi, Markku, Voutilainen, Bob, Georgantas, Graham, Heap, Fedik, Rahimov, Keith, Usiskin, Tim, Lu, Danny, Oh, Kirsi, Kalpala, Melissa, Miller, Linda, Mccarthy, Kari, Eklund, Antti, 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Aarsland, D, Garcia-Gonzalez, P, Abdelnour, C, Alarcón-Martín, E, Alcolea, D, Alegret, M, Alvarez, I, Álvarez, V, Armstrong, N, Tsolaki, A, Antúnez, C, Appollonio, I, Arcaro, M, Archetti, S, Pastor, A, Arosio, B, Athanasiu, L, Bailly, H, Banaj, N, Baquero, M, Barral, S, Beiser, A, Below, J, Benchek, P, Benussi, L, Berr, C, Besse, C, Bessi, V, Binetti, G, Bizarro, A, Blesa, R, Boada, M, Boerwinkle, E, Borroni, B, Boschi, S, Bossù, P, Bråthen, G, Bressler, J, Bresner, C, Brodaty, H, Brookes, K, Brusco, L, Buiza-Rueda, D, Bûrger, K, Burholt, V, Bush, W, Calero, M, Cantwell, L, Chene, G, Chung, J, Cuccaro, M, Carracedo, Á, Cecchetti, R, Cervera-Carles, L, Charbonnier, C, Chen, H, Chillotti, C, Ciccone, S, Claassen, J, Clark, C, Conti, E, Corma-Gómez, A, Costantini, E, Custodero, C, Daian, D, Dalmasso, M, Daniele, A, Dardiotis, E, Dartigues, J, de Deyn, P, de Paiva Lopes, K, de Witte, L, Debette, S, Deckert, J, Del Ser, T, Denning, N, Destefano, A, Dichgans, M, Diehl-Schmid, J, Diez-Fairen, 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Peters, O, Pijnenburg, Y, Pineda, J, Piñol-Ripoll, G, Pisanu, C, Polak, T, Popp, J, Posthuma, D, Priller, J, Puerta, R, Quenez, O, Quintela, I, Thomassen, J, Rábano, A, Rainero, I, Rajabli, F, Ramakers, I, Real, L, Reinders, M, Reitz, C, Reyes-Dumeyer, D, Ridge, P, Riedel-Heller, S, Riederer, P, Roberto, N, Rodriguez-Rodriguez, E, Rongve, A, Allende, I, Rosende-Roca, M, Royo, J, Rubino, E, Rujescu, D, Sáez, M, Sakka, P, Saltvedt, I, Sanabria, Á, Sánchez-Arjona, M, Sanchez-Garcia, F, Juan, P, Sánchez-Valle, R, Sando, S, Sarnowski, C, Satizabal, C, Scamosci, M, Scarmeas, N, Scarpini, E, Scheltens, P, Scherbaum, N, Scherer, M, Schmid, M, Schneider, A, Schott, J, Selbæk, G, Seripa, D, Serrano, M, Sha, J, Shadrin, A, Skrobot, O, Slifer, S, Snijders, G, Soininen, H, Solfrizzi, V, Solomon, A, Song, Y, Sorbi, S, Sotolongo-Grau, O, Spalletta, G, Spottke, A, Squassina, A, Stordal, E, Tartan, J, Tárraga, L, Tesí, N, Thalamuthu, A, Thomas, T, Tosto, G, Traykov, L, Tremolizzo, L, Tybjærg-Hansen, A, Uitterlinden, A, Ullgren, A, Ulstein, I, Valero, S, Valladares, O, Broeckhoven, C, Vance, J, Vardarajan, B, van der Lugt, A, Dongen, J, van Rooij, J, van Swieten, J, Vandenberghe, R, Verhey, F, Vidal, J, Vogelgsang, J, Vyhnalek, M, Wagner, M, Wallon, D, Wang, L, Wang, R, Weinhold, L, Wiltfang, J, Windle, G, Woods, B, Yannakoulia, M, Zare, H, Zhao, Y, Zhang, X, Zhu, C, Zulaica, M, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Farrer, L, Psaty, B, Ghanbari, M, Raj, T, Sachdev, P, Mather, K, Jessen, F, Ikram, M, de Mendonça, A, Hort, J, Tsolaki, M, Pericak-Vance, M, Amouyel, P, Williams, J, Frikke-Schmidt, R, Clarimon, J, Deleuze, J, Rossi, G, Seshadri, S, Andreassen, O, Ingelsson, M, Hiltunen, M, Sleegers, K, Schellenberg, G, van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, VU University medical center, Amsterdam Neuroscience - Neurodegeneration, Neurology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, 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[0000-0002-7542-1139], Kornhuber, Johannes [0000-0002-8096-3987], Kosmidis, Mary H [0000-0001-8790-1220], Lage, Carmen [0000-0003-1703-121X], Launer, Lenore [0000-0002-3238-7612], Lee, Chien-Yueh [0000-0002-4304-974X], Lleó, Alberto [0000-0002-2568-5478], Lopez, Oscar [0000-0002-8546-8256], de Munain, Adolfo Lopez [0000-0002-9509-4032], Lunetta, Kathryn L [0000-0002-9268-810X], Ma, Yiyi [0000-0002-3609-8877], MacLeod, Catherine A [0000-0002-9314-7380], Marquié, Marta [0000-0002-0660-0950], Montes, Angel Martín [0000-0002-1694-786X], Mead, Simon [0000-0002-4326-1468], Medina, Miguel [0000-0002-7016-5340], Menéndez-González, Manuel [0000-0002-5218-0774], Mol, Merel [0000-0003-2533-2530], Morgan, Kevin [0000-0002-8217-2396], Nöthen, Markus M [0000-0002-8770-2464], Muchnik, Carolina [0000-0002-1542-3706], Nacmias, Benedetta [0000-0001-9338-9040], Nicolas, Gael [0000-0001-9391-7800], Nordestgaard, Børge G [0000-0002-1954-7220], Pasquier, Florence [0000-0001-9880-9788], Pastor, Pau [0000-0002-7493-8777], Peloso, Gina [0000-0002-5355-8636], Pérez-Cordón, Alba [0000-0002-6028-0791], Pérez-Tur, Jordi [0000-0002-9111-1712], Pericard, Pierre [0000-0001-8167-6448], Pineda, Juan A [0000-0002-3751-0296], Pisanu, Claudia [0000-0002-9151-4319], Posthuma, Danielle [0000-0001-7582-2365], Puerta, Raquel [0000-0002-1191-5893], Quenez, Olivier [0000-0002-8273-8505], Thomassen, Jesper Qvist [0000-0003-3484-9531], Real, Luis M [0000-0003-4932-7429], Reinders, Marcel JT [0000-0002-1148-1562], Reitz, Christiane [0000-0001-8757-7889], Riedel-Heller, Steffi [0000-0003-4321-6090], Rodriguez-Rodriguez, Eloy [0000-0001-7742-677X], Rongve, Arvid [0000-0002-0476-4134], Sáez, María Eugenia [0000-0001-9299-2534], Saltvedt, Ingvild [0000-0002-7897-9808], Juan, Pascual Sánchez [0000-0002-6081-8037], Sarnowski, Chloé [0000-0002-6090-7099], Satizabal, Claudia L [0000-0002-1115-4430], Schott, Jonathan M [0000-0003-2059-024X], Selbæk, Geir [0000-0001-6511-8219], Shadrin, Alexey A [0000-0002-7467-250X], Soininen, Hilkka [0000-0002-2785-9937], Solfrizzi, Vincenzo [0000-0002-8524-0315], Song, Yeunjoo [0000-0002-7452-3731], Sotolongo-Grau, Oscar [0000-0002-9679-0670], Spalletta, Gianfranco [0000-0002-7432-4249], Squassina, Alessio [0000-0001-7415-7607], Stordal, Eystein [0000-0002-2443-7923], Tosto, Giuseppe [0000-0001-7075-8245], Uitterlinden, Andre [0000-0002-7276-3387], Valladares, Otto [0000-0001-8055-2187], Broeckhoven, Christine Van [0000-0003-0183-7665], Vidal, Jean-Sébastien [0000-0001-6770-0720], Vogelgsang, Jonathan [0000-0001-9326-8193], Wagner, Michael [0000-0003-2589-6440], Wallon, David [0000-0002-2634-7198], Wiltfang, Jens [0000-0003-1492-5330], Woods, Bob [0000-0002-6781-651X], Yannakoulia, Mary [0000-0003-2171-7337], Zare, Habil [0000-0001-5902-6238], Zhang, Xiaoling [0000-0001-8237-1857], Farrer, Lindsay A [0000-0001-5533-4225], Psaty, Bruce M [0000-0002-7278-2190], Ghanbari, Mohsen [0000-0002-9476-7143], Raj, Towfique [0000-0002-9355-5704], Sachdev, Perminder [0000-0002-9595-3220], Mather, Karen [0000-0003-4143-8941], Ikram, M Arfan [0000-0003-0372-8585], Tsolaki, Magda [0000-0002-2072-8010], Pericak-Vance, Margaret A [0000-0001-7283-8804], Amouyel, Philippe [0000-0001-9088-234X], Williams, Julie [0000-0002-4069-0259], Frikke-Schmidt, Ruth [0000-0003-4084-5027], Seshadri, Sudha [0000-0001-6135-2622], Andreassen, Ole A [0000-0002-4461-3568], Sleegers, Kristel [0000-0002-0283-2332], van Duijn, Cornelia M [0000-0002-2374-9204], Sims, Rebecca [0000-0002-3885-1199], van der Flier, Wiesje M [0000-0001-8766-6224], Ramirez, Alfredo [0000-0003-4991-763X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Complex Trait Genetics, Clinical sciences, Neuroprotection & Neuromodulation, Pathologic Biochemistry and Physiology, Clinical Biology, Epidemiology, Internal Medicine, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
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tau Proteins/genetics ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurologi ,MED/03 - GENETICA MEDICA ,45/43 ,Medizin ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,genetics [Alzheimer Disease] ,Genome-Wide Association Study ,Humans ,tau Proteins ,Alzheimer Disease ,Cognitive Dysfunction ,VARIANTS ,pathology [Alzheimer Disease] ,Tau Proteins ,Settore BIO/13 - Biologia Applicata ,Cognitive Dysfunction/psychology ,692/699/375/365/1283 ,IMPUTATION ,article ,1184 Genetics, developmental biology, physiology ,Biología y Biomedicina / Biología ,AMYLOID-BETA ,Settore MED/26 - NEUROLOGIA ,Neurology ,psychology [Cognitive Dysfunction] ,Medical Genetics ,Human ,Neuroscience(all) ,631/208/205/2138 ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,ddc:570 ,Genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Medicinsk genetik ,MED/26 - NEUROLOGIA ,Alzheimer Disease/genetics ,neurology ,tau Protein ,NECROSIS-FACTOR-ALPHA ,RISK LOCI ,genetics [tau Proteins] ,PREDICTION MODELS ,Human medicine ,GENERATION ,RESPONSES - Abstract
25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
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- 2022
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7. De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies
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Appenzeller, Silke, Balling, Rudi, Barisic, Nina, Baulac, Stéphanie, Caglayan, Hande, Craiu, Dana, De Jonghe, Peter, Depienne, Christel, Dimova, Petia, Djémié, Tania, Gormley, Padhraig, Guerrini, Renzo, Helbig, Ingo, Hjalgrim, Helle, Hoffman-Zacharska, Dorota, Jähn, Johanna, Klein, Karl Martin, Koeleman, Bobby, Komarek, Vladimir, Krause, Roland, Kuhlenbäumer, Gregor, Leguern, Eric, Lehesjoki, Anna-Elina, Lemke, Johannes R., Lerche, Holger, Linnankivi, Tarja, Marini, Carla, May, Patrick, Møller, Rikke S., Muhle, Hiltrud, Pal, Deb, Palotie, Aarno, Pendziwiat, Manuela, Robbiano, Angela, Roelens, Filip, Rosenow, Felix, Selmer, Kaja, Serratosa, Jose M., Sisodiya, Sanjay, Stephani, Ulrich, Sterbova, Katalin, Striano, Pasquale, Suls, Arvid, Talvik, Tiina, von Spiczak, Sarah, Weber, Yvonne, Weckhuysen, Sarah, Zara, Federico, Abou-Khalil, Bassel, Alldredge, Brian K., Andermann, Eva, Andermann, Frederick, Amron, Dina, Bautista, Jocelyn F., Berkovic, Samuel F., Bluvstein, Judith, Boro, Alex, Cascino, Gregory, Consalvo, Damian, Crumrine, Patricia, Devinsky, Orrin, Dlugos, Dennis, Epstein, Michael P., Fiol, Miguel, Fountain, Nathan B., French, Jacqueline, Friedman, Daniel, Geller, Eric B., Glauser, Tracy, Glynn, Simon, Haas, Kevin, Haut, Sheryl R., Hayward, Jean, Helmers, Sandra L., Joshi, Sucheta, Kanner, Andres, Kirsch, Heidi E., Knowlton, Robert C., Kossoff, Eric H., Kuperman, Rachel, Kuzniecky, Ruben, Lowenstein, Daniel H., McGuire, Shannon M., Motika, Paul V., Novotny, Edward J., Ottman, Ruth, Paolicchi, Juliann M., Parent, Jack, Park, Kristen, Poduri, Annapurna, Sadleir, Lynette, Scheffer, Ingrid E., Shellhaas, Renée A., Sherr, Elliott, Shih, Jerry J., Singh, Rani, Sirven, Joseph, Smith, Michael C., Sullivan, Joe, Thio, Liu Lin, Venkat, Anu, Vining, Eileen P.G., Von Allmen, Gretchen K., Weisenberg, Judith L., Widdess-Walsh, Peter, Winawer, Melodie R., Allen, Andrew S., Cossette, Patrick, Delanty, Norman, Eichler, Evan E., Goldstein, David B., Han, Yujun, Heinzen, Erin L., Johnson, Michael R., Marson, Anthony G., Mefford, Heather C., Nieh, Sahar Esmaeeli, O’Brien, Terence J., Petrou, Stephen, Petrovski, Slavé, and Ruzzo, Elizabeth K.
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- 2014
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8. Systematic single-variant and gene-based association testing of thousands of phenotypes in 394,841 UK Biobank exomes
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Konrad J. Karczewski, Matthew Solomonson, Katherine R. Chao, Julia K. Goodrich, Grace Tiao, Wenhan Lu, Bridget M. Riley-Gillis, Ellen A. Tsai, Hye In Kim, Xiuwen Zheng, Fedik Rahimov, Sahar Esmaeeli, A. Jason Grundstad, Mark Reppell, Jeff Waring, Howard Jacob, David Sexton, Paola G. Bronson, Xing Chen, Xinli Hu, Jacqueline I. Goldstein, Daniel King, Christopher Vittal, Timothy Poterba, Duncan S. Palmer, Claire Churchhouse, Daniel P. Howrigan, Wei Zhou, Nicholas A. Watts, Kevin Nguyen, Huy Nguyen, Cara Mason, Christopher Farnham, Charlotte Tolonen, Laura D. Gauthier, Namrata Gupta, Daniel G. MacArthur, Heidi L. Rehm, Cotton Seed, Anthony A. Philippakis, Mark J. Daly, J. Wade Davis, Heiko Runz, Melissa R. Miller, and Benjamin M. Neale
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- 2022
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9. Fragile X syndrome screening of families with consanguineous and non-consanguineous parents in the Iranian population
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Pouya, Ali Reza, Abedini, Seyedeh Sedigheh, Mansoorian, Neda, Behjati, Farkhondeh, Nikzat, Nooshin, Mohseni, Marzieh, Nieh, Sahar Esmaeeli, Abbasi Moheb, Lia, Darvish, Hossein, Monajemi, Gholamreza Bahrami, Banihashemi, Susan, Kahrizi, Kimia, Ropers, Hans Hilger, and Najmabadi, Hossein
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- 2009
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10. Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals
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Martin I. Jones, Joseph D. Szustakowski, Giorgio Sirugo, Lukas Habegger, Adam J. Mansfield, Will Salerno, Joshua D. Backman, Athanasios Kousathanas, David J. Carey, Yi-Pin Lai, James F. Wilson, Alison M. Meynert, Anne E. Justice, Alexander H. Li, Jack A. Kosmicki, Anthony Marcketta, Sándor Szalma, Shane McCarthy, A. R. Shuldiner, A. Baras, Daniel J. Rader, Michael N. Cantor, Ashish Yadav, Manuel A. R. Ferreira, F. S. P. Kury, Konrad Rawlik, Loukas Moutsianas, Gonçalo R. Abecasis, Susan P. Walker, Xing Chen, Albert Tenesa, Paul Nioi, Adam E. Locke, Guillaume Butler-Laporte, E. N. Smith, Richard H Scott, Gundula Povysil, Joseph B. Leader, Lauren Gurski, Dorota Pasko, Marylyn D. Ritchie, A. Cordova-Palomera, Kyoko Watanabe, Colm O'Dushlaine, A. O'Neill, Tomoko Nakanishi, Erola Pairo-Castineira, Xiuwen Zheng, Emily Wong, Jeffrey G. Reid, Slavé Petrovski, Julie E. Horowitz, Anurag Verma, Justin W. Davis, Dylan Sun, Sahar Esmaeeli, Heiko Runz, Quanli Wang, John D. Overton, Shareef Khalid, Tooraj Mirshahi, Evan Maxwell, Mark J. Caulfield, Mark Lathrop, Olympe Chazara, Deepika Sharma, David Goldstein, Jonathan Marchini, Xiaodong Bai, Suganthi Balasubramanian, Krzysztof Kiryluk, Nilanjana Banerjee, Rouel Lanche, J. B. Richards, Hyun Min Kang, J. K. Baillie, Yunfeng Huang, Sean O'Keeffe, Erika Kvikstad, Margaret M. Parker, and Joelle Mbatchou
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Male ,0301 basic medicine ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Biology ,03 medical and health sciences ,Current sample ,0302 clinical medicine ,Data sequences ,Report ,Exome Sequencing ,Genetics ,Humans ,Exome ,Genetic Predisposition to Disease ,030212 general & internal medicine ,Gene ,Genetics (clinical) ,SARS-CoV-2 ,COVID-19 ,Prognosis ,Hospitalization ,030104 developmental biology ,Sample Size ,Multiple comparisons problem ,Susceptibility locus ,Female ,Interferons - Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.
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- 2021
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11. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci
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Najmabadi, Hossein, Motazacker, Mohammad Mahdi, Garshasbi, Masoud, Kahrizi, Kimia, Tzschach, Andreas, Chen, Wei, Behjati, Farkhondeh, Hadavi, Valeh, Nieh, Sahar Esmaeeli, Abedini, Seyedeh Sedigheh, Vazifehmand, Reza, Firouzabadi, Saghar Ghasemi, Jamali, Payman, Falah, Masoumeh, Seifati, Seyed Morteza, Grüters, Annette, Lenzner, Steffen, Jensen, Lars R., Rüschendorf, Franz, Kuss, Andreas W., and Ropers, H. Hilger
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- 2007
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12. SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly
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Garshasbi, Masoud, Motazacker, Mohammad Mahdi, Kahrizi, Kimia, Behjati, Farkhondeh, Abedini, Seyedeh Sedigheh, Nieh, Sahar Esmaeeli, Firouzabadi, Saghar Ghasemi, Becker, Christian, Rüschendorf, Franz, Nürnberg, Peter, Tzschach, Andreas, Vazifehmand, Reza, Erdogan, Fikret, Ullmann, Reinhard, Lenzner, Steffen, Kuss, Andreas W., Ropers, H. Hilger, and Najmabadi, Hossein
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- 2006
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13. A defect in the Ionotropic Glutamate Receptor 6 Gene (GRIK2)is associated with autosomal recessive mental retardation
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Motazacker, Mohammad Mahdi, Ropers, Hans Hilger, Najmabadi, Hossein, Kuss, Andreas Walter, Tzchach, Andreas, Jensen, Lars Riff, Schmitz, Dietmar, Amini, Saeid Hosseini, Goswami, Chandan, Kahrizi, Kimia, Ullmann, Reinhard, Abedini, Sedigheh Seyedeh, Nieh, Sahar Esmaeeli, Rost, Benjamin Rainer, Hucho, Tim, and Garshasbi, Masoud
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Mental retardation -- Genetic aspects ,Gene mutations -- Research ,Biological sciences - Abstract
A report on complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2) with a moderate-to-serve nonsyndromic autosomal recessive mental retardation is presented.
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- 2007
14. De novo mutations in epileptic encephalopathies
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Allen, Andrew S., Cossette, Patrick, Delanty, Norman, Eichler, Evan E., Epstein, Michael P., Glauser, Tracy, Goldstein, David B., Han, Yujun, Heinzen, Erin L., Hitomi, Yuki, Howell, Katherine B., Johnson, Michael R., Kuzniecky, Ruben, Lowenstein, Daniel H., Lu, Yi-Fan, Madou, Maura R. Z., Marson, Anthony G., Mefford, Heather C., Nieh, Sahar Esmaeeli, OʼBrien, Terence J., Ottman, Ruth, Petrovski, Slavé, Poduri, Annapurna, Ruzzo, Elizabeth K., Sherr, Elliott H., Yuskaitis, Christopher J., Abou-Khalil, Bassel, Alldredge, Brian K., Bautista, Jocelyn F., Berkovic, Samuel F., Boro, Alex, Cascino, Gregory D., Consalvo, Damian, Crumrine, Patricia, Devinsky, Orrin, Dlugos, Dennis, Fiol, Miguel, Fountain, Nathan B., French, Jacqueline, Friedman, Daniel, Geller, Eric B., Glynn, Simon, Haut, Sheryl R., Hayward, Jean, Helmers, Sandra L., Joshi, Sucheta, Kanner, Andres, Kirsch, Heidi E., Knowlton, Robert C., Kossoff, Eric H., Kuperman, Rachel, McGuire, Shannon M., Motika, Paul V., Novotny, Edward J., Paolicchi, Juliann M., Parent, Jack M., Park, Kristen, Scheffer, Ingrid E., Shellhaas, Renée A., Shih, Jerry J., Singh, Rani, Sirven, Joseph, Smith, Michael C., Sullivan, Joseph, Thio, Liu Lin, Venkat, Anu, Vining, Eileen P. G., Von Allmen, Gretchen K., Weisenberg, Judith L., Widdess-Walsh, Peter, and Winawer, Melodie R.
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- 2013
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15. De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies
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Silke Appenzeller, Rudi Balling, Nina Barisic, Stéphanie Baulac, Hande Caglayan, Dana Craiu, Peter De Jonghe, Christel Depienne, Petia Dimova, Tania Djémié, Padhraig Gormley, Renzo Guerrini, Ingo Helbig, Helle Hjalgrim, Dorota Hoffman-Zacharska, Johanna Jähn, Karl Martin Klein, Bobby Koeleman, Vladimir Komarek, Roland Krause, Gregor Kuhlenbäumer, Eric Leguern, Anna-Elina Lehesjoki, Johannes R. Lemke, Holger Lerche, Tarja Linnankivi, Carla Marini, Patrick May, Rikke S. Møller, Hiltrud Muhle, Deb Pal, Aarno Palotie, Manuela Pendziwiat, Angela Robbiano, Filip Roelens, Felix Rosenow, Kaja Selmer, Jose M. Serratosa, Sanjay Sisodiya, Ulrich Stephani, Katalin Sterbova, Pasquale Striano, Arvid Suls, Tiina Talvik, Sarah von Spiczak, Yvonne Weber, Sarah Weckhuysen, Federico Zara, Bassel Abou-Khalil, Brian K. Alldredge, Eva Andermann, Frederick Andermann, Dina Amrom, Jocelyn F. Bautista, Samuel F. Berkovic, Judith Bluvstein, Alex Boro, Gregory Cascino, Damian Consalvo, Patricia Crumrine, Orrin Devinsky, Dennis Dlugos, Michael P. Epstein, Miguel Fiol, Nathan B. Fountain, Jacqueline French, Daniel Friedman, Eric B. Geller, Tracy Glauser, Simon Glynn, Kevin Haas, Sheryl R. Haut, Jean Hayward, Sandra L. Helmers, Sucheta Joshi, Andres Kanner, Heidi E. Kirsch, Robert C. Knowlton, Eric H. Kossoff, Rachel Kuperman, Ruben Kuzniecky, Daniel H. Lowenstein, Shannon M. McGuire, Paul V. Motika, Edward J. Novotny, Ruth Ottman, Juliann M. Paolicchi, Jack Parent, Kristen Park, Annapurna Poduri, Lynette Sadleir, Ingrid E. Scheffer, Renée A. Shellhaas, Elliott Sherr, Jerry J. Shih, Rani Singh, Joseph Sirven, Michael C. Smith, Joe Sullivan, Liu Lin Thio, Anu Venkat, Eileen P.G. Vining, Gretchen K. Von Allmen, Judith L. Weisenberg, Peter Widdess-Walsh, Melodie R. Winawer, Andrew S. Allen, Patrick Cossette, Norman Delanty, Evan E. Eichler, David B. Goldstein, Yujun Han, Erin L. Heinzen, Michael R. Johnson, Anthony G. Marson, Heather C. Mefford, Sahar Esmaeeli Nieh, Terence J. O’Brien, Stephen Petrou, Slavé Petrovski, Elizabeth K. Ruzzo, Neuroscience Center, Research Programs Unit, Department of Medical and Clinical Genetics, Research Programme for Molecular Neurology, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, EuroEPINOMICS-RES Consortium, Epilepsy Phenome Genome Project, and Epi4K Consortium
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0301 basic medicine ,Male ,Proband ,INTELLECTUAL DISABILITY ,Type I ,Bioinformatics ,medicine.disease_cause ,Infantile ,Synaptic Transmission ,Spasms ,Cohort Studies ,Epilepsy ,0302 clinical medicine ,Receptors ,SCHIZOPHRENIA ,STXBP1 ,Exome ,Gene Regulatory Networks ,Protein Interaction Maps ,Dynamin I ,Genetics (clinical) ,Genetics ,0303 health sciences ,Mutation ,education.field_of_study ,Medicine (all) ,Genome project ,Fatty Acid Synthase, Type I ,Fatty Acid Synthase ,Female ,APHASIA ,Spasms, Infantile ,DYNAMIN-1 ,EPILEPSIES ,ENDOCYTOSIS ,Population ,SPECTRUM DISORDERS ,Phenome ,Neurotransmission ,Biology ,GNAO1 ,Article ,03 medical and health sciences ,GRIN2A MUTATIONS ,medicine ,Humans ,AUTISM ,Infant, Newborn ,Lennox Gastaut Syndrome ,Receptors, GABA-B ,Ryanodine Receptor Calcium Release Channel ,education ,Gene ,De novo mutations ,030304 developmental biology ,GABA-B ,3112 Neurosciences ,Infant ,Correction ,Newborn ,medicine.disease ,Human genetics ,030104 developmental biology ,DNM1 ,PATTERNS ,Human medicine ,030217 neurology & neurosurgery ,Lennox–Gastaut syndrome - Abstract
Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de nova mutations, including de novo mutations in DNM1 in five individuals and de nova mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de nova mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 x 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de nova mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction.
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- 2017
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16. Erratum : De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies (American Journal of Human Genetics (2014) 95(4) (360–370)(S0002929714003838)(10.1016/j.ajhg.2014.08.013))
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Appenzeller, Silke, Balling, Rudi, Barisic, Nina, Baulac, Stéphanie, Caglayan, Hande, Craiu, Dana, De Jonghe, Peter, Depienne, Christel, Dimova, Petia, Djémié, Tania, Gormley, Padhraig, Guerrini, Renzo, Helbig, Ingo, Hjalgrim, Helle, Hoffman-Zacharska, Dorota, Jähn, Johanna A., Klein, Karl Martin, Koeleman, Bobby, Komarek, Vladimir, Krause, Roland, Kuhlenbäumer, Gregor, Leguern, Eric, Lehesjoki, Anna-Elina, Lemke, Johannes R., Lerche, Holger, Linnankivi, Tarja, Marini, Carla, May, Patrick, Møller, Rikke S., Muhle, Hiltrud, Pal, Deb, Palotie, Aarno, Pendziwiat, Manuela, Robbiano, Angela, Roelens, Filip, Rosenow, Felix, Selmer, Kaja, Serratosa, Jose M., Sisodiya, Sanjay M., Stephani, Ulrich, Sterbova, Katalin, Striano, Pasquale, Suls, Arvid, Talvik, Tiina, von Spiczak, Sarah, Weber, Yvonne G., Weckhuysen, Sarah, Zara, Federico, Abou-Khalil, Bassel, Alldredge, Brian K., Andermann, Eva, Andermann, Frederick, Amrom, Dina, Bautista, Jocelyn F., Berkovic, Samuel F., Bluvstein, Judith, Boro, Alex, Cascino, Gregory, Consalvo, Damian, Crumrine, Patricia, Devinsky, Orrin, Dlugos, Dennis, Epstein, Michael P., Fiol, Miguel, Fountain, Nathan B., French, Jacqueline, Friedman, Daniel, Geller, Eric B., Glauser, Tracy, Glynn, Simon, Haas, Kevin, Haut, Sheryl R., Hayward, Jean, Helmers, Sandra L., Joshi, Sucheta, Kanner, Andres, Kirsch, Heidi E., Knowlton, Robert C., Kossoff, Eric H., Kuperman, Rachel, Kuzniecky, Ruben, Lowenstein, Daniel H., McGuire, Shannon M., Motika, Paul V., Novotny, Edward J., Ottman, Ruth, Paolicchi, Juliann M., Parent, Jack, Park, Kristen, Poduri, Annapurna, Sadleir, Lynette G., Scheffer, Ingrid E., Shellhaas, Renée A, Sherr, Elliott, Shih, Jerry J., Singh, Rani, Sirven, Joseph, Smith, Michael C., Sullivan, Joe, Thio, Liu Lin, Venkat, Anu, Vining, Eileen P. G., Von Allmen, Gretchen K., Weisenberg, Judith L., Widdess-Walsh, Peter, Winawer, Melodie R., Allen, Andrew S., Cossette, Patrick, Delanty, Norman, Eichler, Evan E., Goldstein, David B., Han, Yujun, Heinzen, Erin L., Johnson, Michael R., Marson, Anthony G., Mefford, Heather C., Nieh, Sahar Esmaeeli, O'Brien, Terence J., Petrou, Stephen, Petrovski, Slavé, and Ruzzo, Elizabeth K.
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Genetics ,Genetics(clinical) - Abstract
(The American Journal of Human Genetics 95, 360–370; October 2, 2014) In the list of consortium members for the Epilepsy Phenome/Genome Project, member Dina Amrom's name was misspelled as Amron. The authors regret the error.
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- 2017
17. Epileptic encephalopathies: new genes and new pathways.
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Nieh, Sahar Esmaeeli, Nieh, Sahar Esmaeeli, Sherr, Elliott H, Nieh, Sahar Esmaeeli, Nieh, Sahar Esmaeeli, and Sherr, Elliott H
- Abstract
Epileptic encephalopathies represent a group of devastating epileptic disorders that occur early in life and are often characterized by pharmaco-resistant epilepsy, persistent severe electroencephalographic abnormalities, and cognitive dysfunction or decline. Next generation sequencing technologies have increased the speed of gene discovery tremendously. Whereas ion channel genes were long considered to be the only significant group of genes implicated in the genetic epilepsies, a growing number of non-ion-channel genes are now being identified. As a subgroup of the genetically mediated epilepsies, epileptic encephalopathies are complex and heterogeneous disorders, making diagnosis and treatment decisions difficult. Recent exome sequencing data suggest that mutations causing epileptic encephalopathies are often sporadic, typically resulting from de novo dominant mutations in a single autosomal gene, although inherited autosomal recessive and X-linked forms also exist. In this review we provide a summary of the key features of several early- and mid-childhood onset epileptic encephalopathies including Ohtahara syndrome, Dravet syndrome, Infantile spasms and Lennox Gastaut syndrome. We review the recent next generation sequencing findings that may impact treatment choices. We also describe the use of conventional and newer anti-epileptic and hormonal medications in the various syndromes based on their genetic profile. At a biological level, developments in cellular reprogramming and genome editing represent a new direction in modeling these pediatric epilepsies and could be used in the development of novel and repurposed therapies.
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- 2014
18. BOD1 Is Required for Cognitive Function in Humans and Drosophila
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M. Mahdi Motazacker, Hossein Najmabadi, Farkhondeh Behjati, Sahar Esmaeeli-Nieh, Zoltan Asztalos, Harry Scherthan, Andreas W. Kuss, Andreas Tzschach, Michaela Fenckova, Seyed Morteza Sayfati, Iain M. Porter, Robert Weißmann, Anna Castells-Nobau, Kimia Kahrizi, Bonnie Nijhof, Jason R. Swedlow, Ute Felbor, Hans-Hilger Ropers, Annette Schenck, Amsterdam Cardiovascular Sciences, Human Genetics, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms
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0301 basic medicine ,Cancer Research ,Physiology ,Cell Cycle Proteins ,medicine.disease_cause ,Biochemistry ,Nervous System ,Mice ,0302 clinical medicine ,Cognition ,RNA interference ,Animal Cells ,Chromosome Segregation ,Medicine and Health Sciences ,Small interfering RNAs ,Protein Phosphatase 2 ,Cell Cycle and Cell Division ,Genetics (clinical) ,Connective Tissue Cells ,Regulation of gene expression ,Neurons ,Gene knockdown ,Mutation ,Chromosome Biology ,Drosophila Melanogaster ,Animal Models ,Cell cycle ,Cell biology ,Insects ,Nucleic acids ,Electrophysiology ,Genetic interference ,Connective Tissue ,Cell Processes ,Gene Knockdown Techniques ,Drosophila ,Epigenetics ,Cellular Types ,Anatomy ,Research Article ,Arthropoda ,lcsh:QH426-470 ,Mitosis ,Neurophysiology ,Biology ,Protein Serine-Threonine Kinases ,Research and Analysis Methods ,PLK1 ,03 medical and health sciences ,Model Organisms ,Proto-Oncogene Proteins ,medicine ,Genetics ,Animals ,Humans ,Learning ,Cell Cycle Protein ,Non-coding RNA ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Organisms ,Biology and Life Sciences ,Protein phosphatase 2 ,Cell Biology ,Fibroblasts ,Invertebrates ,Gene regulation ,lcsh:Genetics ,030104 developmental biology ,Biological Tissue ,Gene Expression Regulation ,Cellular Neuroscience ,Synapses ,RNA ,Gene expression ,030217 neurology & neurosurgery ,HeLa Cells ,Neuroscience - Abstract
Here we report a stop-mutation in the BOD1 (Biorientation Defective 1) gene, which co-segregates with intellectual disability in a large consanguineous family, where individuals that are homozygous for the mutation have no detectable BOD1 mRNA or protein. The BOD1 protein is required for proper chromosome segregation, regulating phosphorylation of PLK1 substrates by modulating Protein Phosphatase 2A (PP2A) activity during mitosis. We report that fibroblast cell lines derived from homozygous BOD1 mutation carriers show aberrant localisation of the cell cycle kinase PLK1 and its phosphatase PP2A at mitotic kinetochores. However, in contrast to the mitotic arrest observed in BOD1-siRNA treated HeLa cells, patient-derived cells progressed through mitosis with no apparent segregation defects but at an accelerated rate compared to controls. The relatively normal cell cycle progression observed in cultured cells is in line with the absence of gross structural brain abnormalities in the affected individuals. Moreover, we found that in normal adult brain tissues BOD1 expression is maintained at considerable levels, in contrast to PLK1 expression, and provide evidence for synaptic localization of Bod1 in murine neurons. These observations suggest that BOD1 plays a cell cycle-independent role in the nervous system. To address this possibility, we established two Drosophila models, where neuron-specific knockdown of BOD1 caused pronounced learning deficits and significant abnormalities in synapse morphology. Together our results reveal novel postmitotic functions of BOD1 as well as pathogenic mechanisms that strongly support a causative role of BOD1 deficiency in the aetiology of intellectual disability. Moreover, by demonstrating its requirement for cognitive function in humans and Drosophila we provide evidence for a conserved role of BOD1 in the development and maintenance of cognitive features., Author Summary Intellectual disability (ID) is a form of cognitive impairment characterized by limitations in cognitive functions that manifest as an intelligence quotient (IQ) below 70. ID has a prevalence of 1–3% in the general population and represents a major health-care problem. To understand the functional consequences of causative mutations we study the disease-causing mechanisms of hereditary acquired mutations that result in ID. Here we describe a large family that has a mutation affecting a gene called BOD1. Family members who are homozygous for the mutation (i.e. both maternal and paternal copies of the gene carry the mutation) produce no detectable BOD1 protein and suffer from intellectual disability. We have previously shown that BOD1 is a crucial regulator of an important signalling molecule called Protein Phosphatase 2A (PP2A) during cell division. PP2A also has diverse but poorly understood roles in neuronal function. We demonstrate here that Bod1 can regulate PP2A function throughout the cell cycle and also localises to synapses in neurons. To determine if BOD1 deficiency directly affects the structure and function of neurons we targeted the gene in the model fly organism Drosophila Melanogaster. Neuron-specific knockdown caused pronounced learning difficulties and significant abnormalities in synaptic morphology indicating that BOD1 is involved in an evolutionary conserved mechanism crucial for the development of cognitive features.
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- 2016
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19. A Defect in the Ionotropic Glutamate Receptor 6 Gene (GRIK2) Is Associated with Autosomal Recessive Mental Retardation
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Hossein Najmabadi, Andreas Tzschach, Lars Riff Jensen, Saeid Hosseini Amini, Chandan Goswami, Kimia Kahrizi, Sahar Esmaeeli Nieh, Tim Hucho, Andreas W. Kuss, Hans-Hilger Ropers, M. Mahdi Motazacker, Seyedeh Sedigheh Abedini, Reinhard Ullmann, Benjamin R. Rost, Masoud Garshasbi, Dietmar Schmitz, and Experimental Vascular Medicine
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Adult ,Male ,Models, Molecular ,DNA, Complementary ,Protein Conformation ,Genes, Recessive ,Kainate receptor ,Biology ,Transfection ,medicine.disease_cause ,Cell Line ,Gene product ,Consanguinity ,Receptors, Kainic Acid ,GRIK2 ,Intellectual Disability ,Report ,Genetics ,medicine ,Humans ,Genetics(clinical) ,Genetics (clinical) ,Loss function ,Mutation ,Base Sequence ,Middle Aged ,Recombinant Proteins ,Pedigree ,Transmembrane domain ,Italy ,biology.protein ,Ionotropic glutamate receptor ,Female ,Ionotropic effect - Abstract
Nonsyndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked forms, but, in contrast to the latter, they are still largely unexplored. Here, we report a complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2, also called "GLUR6") that cosegregates with moderate-to-severe nonsyndromic autosomal recessive mental retardation in a large, consanguineous Iranian family. The predicted gene product lacks the first ligand-binding domain, the adjacent transmembrane domain, and the putative pore loop, suggesting a complete loss of function of the GLU(K6) protein, which is supported by electrophysiological data. This finding provides the first proof that GLU(K6) is indispensable for higher brain functions in humans, and future studies of this and other ionotropic kainate receptors will shed more light on the pathophysiology of mental retardation.
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- 2007
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20. De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy
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Luba Blumkin, Dianalee McKnight, Elliott H. Sherr, Marie T. McDonald, Sahar Esmaeeli Nieh, Katrina W. Lexa, Jonathan B. Strober, Christine G. Spaeth, Maura Madou, Nizar Smaoui, John Pappas, Thomas A. Burrow, Barbara Hallinan, Dorit Lev, Minhajuddin Sirajuddin, Esther Leshinsky-Silver, A. J. Barkovich, Ronald D. Vale, Brieana Fregeau, and Mariam Latibashvili
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Microcephaly ,Pathology ,medicine.medical_specialty ,Ataxia ,business.industry ,General Neuroscience ,medicine.disease ,Hypotonia ,Peripheral neuropathy ,Atrophy ,medicine ,Cerebellar atrophy ,Neurology (clinical) ,Global developmental delay ,medicine.symptom ,business ,Research Articles ,KIF1A - Abstract
Objective: To determine the cause and course of a novel syndrome with progressive encephalopathy and brain atrophy in children. Methods: Clinical whole-exome sequencing was performed for global developmental delay and intellectual disability; some patients also had spastic paraparesis and evidence of clinical regression. Six patients were identified with de novo missense mutations in the kinesin gene KIF1A. The predicted functional disruption of these mutations was assessed in silico to compare the calculated conformational flexibility and estimated efficiency of ATP binding to kinesin motor domains of wild-type (WT) versus mutant alle les. Additionally, an in vitro microtubule gliding assay was performed to assess the effects of de novo dominant, inherited recessive, and polymorphic variants on KIF1A motor function. Results: All six subjects had severe developmental delay, hypotonia, and varying degrees of hyperreflexia and spastic paraparesis. Microcephaly, cortical visual impairment, optic neuropathy, peripheral neuropathy, ataxia, epilepsy, and movement disorders were also observed. All six patients had a degenerative neurologic course with progressivecerebral and cerebellar atrophy seen on sequential magnetic resonance imaging scans. Computational modeling of mutant protein structures when compared to WT kinesin showed substantial differences in conformational flexibility and ATP-binding efficiency. The de novo KIF1A mutants were nonmotile in the microtubule gliding assay. Interpretation :D e novo mutations inKIF1A cause a degenerative neurologic syndrome with brain atrophy. Computational and in vitro assays differentiate the severity of dominant de novo heterozygous versus inherited recessive KIF1A mutations. The profound effect de novo mutations have on axonal transport is likely related to the cause of progressive neurologic impairment in these patients.
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- 2015
21. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci
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Seyed Morteza Seifati, Andreas Tzschach, Masoumeh Falah, Hans-Hilger Ropers, Payman Jamali, Hossein Najmabadi, Reza Vazifehmand, Wei Chen, Valeh Hadavi, Franz Rüschendorf, Lars Riff Jensen, Sahar Esmaeeli Nieh, Annette Grüters, Masoud Garshasbi, Andreas W. Kuss, M. Mahdi Motazacker, Steffen Lenzner, Seyedeh Sedigheh Abedini, Kimia Kahrizi, Saghar Ghasemi Firouzabadi, and Farkhondeh Behjati
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Adult ,Genetic Markers ,Male ,Genes, Recessive ,Locus (genetics) ,Consanguinity ,Iran ,Biology ,Genetic Heterogeneity ,Gene mapping ,Intellectual Disability ,Genetics ,Humans ,Family ,Child ,Genetics (clinical) ,Autosome ,Genetic heterogeneity ,Homozygote ,Disease gene identification ,Human genetics ,Pedigree ,Genetic marker ,Female - Abstract
Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases.
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- 2006
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22. De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies.
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Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], Appenzeller, Silke, Balling, Rudi, Barisic, Nina, Baulac, Stéphanie, Caglayan, Hande, Craiu, Dana, Jonghe, Peter De, Depienne, Christel, Dimova, Petia, Djémié, Tania, Gormley, Padhraig, Guerrini, Renzo, Helbig, Ingo, Hjalgrim, Helle, Hoffman-Zacharska, Dorota, Jähn, Johanna, Klein, Karl Martin, Koeleman, Bobby, Komarek, Vladimir, Krause, Roland, Kuhlenbäumer, Gregor, Leguern, Eric, Lehesjoki, Anna-Elina, Lemke, Johannes R., Lerche, Holger, Linnankivi, Tarja, Marini, Carla, May, Patrick, Møller, Rikke S., Muhle, Hiltrud, Pal, Deb, Palotie, Aarno, Pendziwiat, Manuela, Robbiano, Angela, Roelens, Filip, Rosenow, Felix, Selmer, Kaja, Serratosa, Jose M., Sisodiya, Sanjay, Stephani, Ulrich, Sterbova, Katalin, Striano, Pasquale, Suls, Arvid, Talvik, Tiina, Spiczak, Sarah Von, Weber, Yvonne, Weckhuysen, Sarah, Zara, Federico, Abou-Khalil, Bassel, Alldredge, Brian K., Andermann, Eva, Andermann, Frederick, Amrom, Dina, Bautista, Jocelyn F., Berkovic, Samuel F., Bluvstein, Judith, Boro, Alex, Cascino, Gregory, Consalvo, Damian, Crumrine, Patricia, Devinsky, Orrin, Dlugos, Dennis, Epstein, Michael P., Fiol, Miguel, Fountain, Nathan B., French, Jacqueline, Friedman, Daniel, Geller, Eric B., Glauser, Tracy, Glynn, Simon, Haas, Kevin, Haut, Sheryl R., Hayward, Jean, Helmers, Sandra L., Joshi, Sucheta, Kanner, Andres, Kirsch, Heidi E., Knowlton, Robert C., Kossoff, Eric H., Kuperman, Rachel, Kuzniecky, Ruben, Lowenstein, Daniel H., McGuire, Shannon M., Motika, Paul V., Novotny, Edward J., Ottman, Ruth, Paolicchi, Juliann M., Parent, Jack, Park, Kristen, Poduri, Annapurna, Sadleir, Lynette, Scheffer, Ingrid E., Shellhaas, Renée A., Sherr, Elliott, Shih, Jerry J., Singh, Rani, Sirven, Joseph, Smith, Michael C., Sullivan, Joe, Thio, Liu Lin, Venkat, Anu, Vining, Eileen P. G., Allmen, Gretchen K. Von, Weisenberg, Judith L., Widdess-Walsh, Peter, Winawer, Melodie R., Allen, Andrew S., Cossette, Patrick, Delanty, Norman, Eichler, Evan E., Goldstein, David B., Han, Yujun, Heinzen, Erin L., Johnson, Michael R., Marson, Anthony G., Mefford, Heather C., Nieh, Sahar Esmaeeli, O’Brien, Terence J., Petrou, Stephen, Petrovski, Slavé, Ruzzo, Elizabeth K., Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], Appenzeller, Silke, Balling, Rudi, Barisic, Nina, Baulac, Stéphanie, Caglayan, Hande, Craiu, Dana, Jonghe, Peter De, Depienne, Christel, Dimova, Petia, Djémié, Tania, Gormley, Padhraig, Guerrini, Renzo, Helbig, Ingo, Hjalgrim, Helle, Hoffman-Zacharska, Dorota, Jähn, Johanna, Klein, Karl Martin, Koeleman, Bobby, Komarek, Vladimir, Krause, Roland, Kuhlenbäumer, Gregor, Leguern, Eric, Lehesjoki, Anna-Elina, Lemke, Johannes R., Lerche, Holger, Linnankivi, Tarja, Marini, Carla, May, Patrick, Møller, Rikke S., Muhle, Hiltrud, Pal, Deb, Palotie, Aarno, Pendziwiat, Manuela, Robbiano, Angela, Roelens, Filip, Rosenow, Felix, Selmer, Kaja, Serratosa, Jose M., Sisodiya, Sanjay, Stephani, Ulrich, Sterbova, Katalin, Striano, Pasquale, Suls, Arvid, Talvik, Tiina, Spiczak, Sarah Von, Weber, Yvonne, Weckhuysen, Sarah, Zara, Federico, Abou-Khalil, Bassel, Alldredge, Brian K., Andermann, Eva, Andermann, Frederick, Amrom, Dina, Bautista, Jocelyn F., Berkovic, Samuel F., Bluvstein, Judith, Boro, Alex, Cascino, Gregory, Consalvo, Damian, Crumrine, Patricia, Devinsky, Orrin, Dlugos, Dennis, Epstein, Michael P., Fiol, Miguel, Fountain, Nathan B., French, Jacqueline, Friedman, Daniel, Geller, Eric B., Glauser, Tracy, Glynn, Simon, Haas, Kevin, Haut, Sheryl R., Hayward, Jean, Helmers, Sandra L., Joshi, Sucheta, Kanner, Andres, Kirsch, Heidi E., Knowlton, Robert C., Kossoff, Eric H., Kuperman, Rachel, Kuzniecky, Ruben, Lowenstein, Daniel H., McGuire, Shannon M., Motika, Paul V., Novotny, Edward J., Ottman, Ruth, Paolicchi, Juliann M., Parent, Jack, Park, Kristen, Poduri, Annapurna, Sadleir, Lynette, Scheffer, Ingrid E., Shellhaas, Renée A., Sherr, Elliott, Shih, Jerry J., Singh, Rani, Sirven, Joseph, Smith, Michael C., Sullivan, Joe, Thio, Liu Lin, Venkat, Anu, Vining, Eileen P. G., Allmen, Gretchen K. Von, Weisenberg, Judith L., Widdess-Walsh, Peter, Winawer, Melodie R., Allen, Andrew S., Cossette, Patrick, Delanty, Norman, Eichler, Evan E., Goldstein, David B., Han, Yujun, Heinzen, Erin L., Johnson, Michael R., Marson, Anthony G., Mefford, Heather C., Nieh, Sahar Esmaeeli, O’Brien, Terence J., Petrou, Stephen, Petrovski, Slavé, and Ruzzo, Elizabeth K.
- Abstract
In the list of consortium members for the Epilepsy Phenome/Genome Project, member Dina Amrom’s name was misspelled as Amron. The authors regret the error.
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- 2017
23. Erratum: De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies (American Journal of Human Genetics (2014) 95(4) (360–370)(S0002929714003838)(10.1016/j.ajhg.2014.08.013))
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Genetica Groep Koeleman, Circulatory Health, Brain, Child Health, Appenzeller, Silke, Balling, Rudi, Barisic, Nina, Baulac, Stéphanie, Caglayan, Hande, Craiu, Dana, De Jonghe, Peter, Depienne, Christel, Dimova, Petia, Djémié, Tania, Gormley, Padhraig, Guerrini, Renzo, Helbig, Ingo, Hjalgrim, Helle, Hoffman-Zacharska, Dorota, Jähn, Johanna A., Klein, Karl Martin, Koeleman, Bobby, Komarek, Vladimir, Krause, Roland, Kuhlenbäumer, Gregor, Leguern, Eric, Lehesjoki, Anna-Elina, Lemke, Johannes R., Lerche, Holger, Linnankivi, Tarja, Marini, Carla, May, Patrick, Møller, Rikke S., Muhle, Hiltrud, Pal, Deb, Palotie, Aarno, Pendziwiat, Manuela, Robbiano, Angela, Roelens, Filip, Rosenow, Felix, Selmer, Kaja, Serratosa, Jose M., Sisodiya, Sanjay M., Stephani, Ulrich, Sterbova, Katalin, Striano, Pasquale, Suls, Arvid, Talvik, Tiina, von Spiczak, Sarah, Weber, Yvonne G., Weckhuysen, Sarah, Zara, Federico, Abou-Khalil, Bassel, Alldredge, Brian K., Andermann, Eva, Andermann, Frederick, Amrom, Dina, Bautista, Jocelyn F., Berkovic, Samuel F., Bluvstein, Judith, Boro, Alex, Cascino, Gregory, Consalvo, Damian, Crumrine, Patricia, Devinsky, Orrin, Dlugos, Dennis, Epstein, Michael P., Fiol, Miguel, Fountain, Nathan B., French, Jacqueline, Friedman, Daniel, Geller, Eric B., Glauser, Tracy, Glynn, Simon, Haas, Kevin, Haut, Sheryl R., Hayward, Jean, Helmers, Sandra L., Joshi, Sucheta, Kanner, Andres, Kirsch, Heidi E., Knowlton, Robert C., Kossoff, Eric H., Kuperman, Rachel, Kuzniecky, Ruben, Lowenstein, Daniel H., McGuire, Shannon M., Motika, Paul V., Novotny, Edward J., Ottman, Ruth, Paolicchi, Juliann M., Parent, Jack, Park, Kristen, Poduri, Annapurna, Sadleir, Lynette G., Scheffer, Ingrid E., Shellhaas, Renée A, Sherr, Elliott, Shih, Jerry J., Singh, Rani, Sirven, Joseph, Smith, Michael C., Sullivan, Joe, Thio, Liu Lin, Venkat, Anu, Vining, Eileen P. G., Von Allmen, Gretchen K., Weisenberg, Judith L., Widdess-Walsh, Peter, Winawer, Melodie R., Allen, Andrew S., Cossette, Patrick, Delanty, Norman, Eichler, Evan E., Goldstein, David B., Han, Yujun, Heinzen, Erin L., Johnson, Michael R., Marson, Anthony G., Mefford, Heather C., Nieh, Sahar Esmaeeli, O'Brien, Terence J., Petrou, Stephen, Petrovski, Slavé, Ruzzo, Elizabeth K., Genetica Groep Koeleman, Circulatory Health, Brain, Child Health, Appenzeller, Silke, Balling, Rudi, Barisic, Nina, Baulac, Stéphanie, Caglayan, Hande, Craiu, Dana, De Jonghe, Peter, Depienne, Christel, Dimova, Petia, Djémié, Tania, Gormley, Padhraig, Guerrini, Renzo, Helbig, Ingo, Hjalgrim, Helle, Hoffman-Zacharska, Dorota, Jähn, Johanna A., Klein, Karl Martin, Koeleman, Bobby, Komarek, Vladimir, Krause, Roland, Kuhlenbäumer, Gregor, Leguern, Eric, Lehesjoki, Anna-Elina, Lemke, Johannes R., Lerche, Holger, Linnankivi, Tarja, Marini, Carla, May, Patrick, Møller, Rikke S., Muhle, Hiltrud, Pal, Deb, Palotie, Aarno, Pendziwiat, Manuela, Robbiano, Angela, Roelens, Filip, Rosenow, Felix, Selmer, Kaja, Serratosa, Jose M., Sisodiya, Sanjay M., Stephani, Ulrich, Sterbova, Katalin, Striano, Pasquale, Suls, Arvid, Talvik, Tiina, von Spiczak, Sarah, Weber, Yvonne G., Weckhuysen, Sarah, Zara, Federico, Abou-Khalil, Bassel, Alldredge, Brian K., Andermann, Eva, Andermann, Frederick, Amrom, Dina, Bautista, Jocelyn F., Berkovic, Samuel F., Bluvstein, Judith, Boro, Alex, Cascino, Gregory, Consalvo, Damian, Crumrine, Patricia, Devinsky, Orrin, Dlugos, Dennis, Epstein, Michael P., Fiol, Miguel, Fountain, Nathan B., French, Jacqueline, Friedman, Daniel, Geller, Eric B., Glauser, Tracy, Glynn, Simon, Haas, Kevin, Haut, Sheryl R., Hayward, Jean, Helmers, Sandra L., Joshi, Sucheta, Kanner, Andres, Kirsch, Heidi E., Knowlton, Robert C., Kossoff, Eric H., Kuperman, Rachel, Kuzniecky, Ruben, Lowenstein, Daniel H., McGuire, Shannon M., Motika, Paul V., Novotny, Edward J., Ottman, Ruth, Paolicchi, Juliann M., Parent, Jack, Park, Kristen, Poduri, Annapurna, Sadleir, Lynette G., Scheffer, Ingrid E., Shellhaas, Renée A, Sherr, Elliott, Shih, Jerry J., Singh, Rani, Sirven, Joseph, Smith, Michael C., Sullivan, Joe, Thio, Liu Lin, Venkat, Anu, Vining, Eileen P. G., Von Allmen, Gretchen K., Weisenberg, Judith L., Widdess-Walsh, Peter, Winawer, Melodie R., Allen, Andrew S., Cossette, Patrick, Delanty, Norman, Eichler, Evan E., Goldstein, David B., Han, Yujun, Heinzen, Erin L., Johnson, Michael R., Marson, Anthony G., Mefford, Heather C., Nieh, Sahar Esmaeeli, O'Brien, Terence J., Petrou, Stephen, Petrovski, Slavé, and Ruzzo, Elizabeth K.
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- 2017
24. De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies
- Author
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Appenzeller, Silke, primary, Balling, Rudi, additional, Barisic, Nina, additional, Baulac, Stéphanie, additional, Caglayan, Hande, additional, Craiu, Dana, additional, De Jonghe, Peter, additional, Depienne, Christel, additional, Dimova, Petia, additional, Djémié, Tania, additional, Gormley, Padhraig, additional, Guerrini, Renzo, additional, Helbig, Ingo, additional, Hjalgrim, Helle, additional, Hoffman-Zacharska, Dorota, additional, Jähn, Johanna, additional, Klein, Karl Martin, additional, Koeleman, Bobby, additional, Komarek, Vladimir, additional, Krause, Roland, additional, Kuhlenbäumer, Gregor, additional, Leguern, Eric, additional, Lehesjoki, Anna-Elina, additional, Lemke, Johannes R., additional, Lerche, Holger, additional, Linnankivi, Tarja, additional, Marini, Carla, additional, May, Patrick, additional, Møller, Rikke S., additional, Muhle, Hiltrud, additional, Pal, Deb, additional, Palotie, Aarno, additional, Pendziwiat, Manuela, additional, Robbiano, Angela, additional, Roelens, Filip, additional, Rosenow, Felix, additional, Selmer, Kaja, additional, Serratosa, Jose M., additional, Sisodiya, Sanjay, additional, Stephani, Ulrich, additional, Sterbova, Katalin, additional, Striano, Pasquale, additional, Suls, Arvid, additional, Talvik, Tiina, additional, von Spiczak, Sarah, additional, Weber, Yvonne, additional, Weckhuysen, Sarah, additional, Zara, Federico, additional, Abou-Khalil, Bassel, additional, Alldredge, Brian K., additional, Andermann, Eva, additional, Andermann, Frederick, additional, Amrom, Dina, additional, Bautista, Jocelyn F., additional, Berkovic, Samuel F., additional, Bluvstein, Judith, additional, Boro, Alex, additional, Cascino, Gregory, additional, Consalvo, Damian, additional, Crumrine, Patricia, additional, Devinsky, Orrin, additional, Dlugos, Dennis, additional, Epstein, Michael P., additional, Fiol, Miguel, additional, Fountain, Nathan B., additional, French, Jacqueline, additional, Friedman, Daniel, additional, Geller, Eric B., additional, Glauser, Tracy, additional, Glynn, Simon, additional, Haas, Kevin, additional, Haut, Sheryl R., additional, Hayward, Jean, additional, Helmers, Sandra L., additional, Joshi, Sucheta, additional, Kanner, Andres, additional, Kirsch, Heidi E., additional, Knowlton, Robert C., additional, Kossoff, Eric H., additional, Kuperman, Rachel, additional, Kuzniecky, Ruben, additional, Lowenstein, Daniel H., additional, McGuire, Shannon M., additional, Motika, Paul V., additional, Novotny, Edward J., additional, Ottman, Ruth, additional, Paolicchi, Juliann M., additional, Parent, Jack, additional, Park, Kristen, additional, Poduri, Annapurna, additional, Sadleir, Lynette, additional, Scheffer, Ingrid E., additional, Shellhaas, Renée A., additional, Sherr, Elliott, additional, Shih, Jerry J., additional, Singh, Rani, additional, Sirven, Joseph, additional, Smith, Michael C., additional, Sullivan, Joe, additional, Thio, Liu Lin, additional, Venkat, Anu, additional, Vining, Eileen P.G., additional, Von Allmen, Gretchen K., additional, Weisenberg, Judith L., additional, Widdess-Walsh, Peter, additional, Winawer, Melodie R., additional, Allen, Andrew S., additional, Cossette, Patrick, additional, Delanty, Norman, additional, Eichler, Evan E., additional, Goldstein, David B., additional, Han, Yujun, additional, Heinzen, Erin L., additional, Johnson, Michael R., additional, Marson, Anthony G., additional, Mefford, Heather C., additional, Nieh, Sahar Esmaeeli, additional, O’Brien, Terence J., additional, Petrou, Stephen, additional, Petrovski, Slavé, additional, and Ruzzo, Elizabeth K., additional
- Published
- 2017
- Full Text
- View/download PDF
25. Mutations in NSUN2 cause autosomal-recessive intellectual disability
- Author
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Sebahattin Cirak, Sahar Esmaeeli-Nieh, Kirsten Cremer, Kimia Kahrizi, Sara Mertel, Hossein Najmabadi, Lia Abbasi-Moheb, M. Mahdi Motazacker, Andreas W. Kuss, Hans-Hilger Ropers, Leyla Nouri-Vahid, Melanie Gonsior, Masoud Garshasbi, Seyedeh Sedigheh Abedini, Stephan J. Sigrist, Robert Weißmann, Dagmar Wieczorek, and Andreas Tzschach
- Subjects
Adult ,Male ,Adolescent ,Genotype ,Genetic Linkage ,Nonsense mutation ,Medizin ,Locus (genetics) ,Genes, Recessive ,Consanguinity ,Article ,03 medical and health sciences ,Exon ,Young Adult ,0302 clinical medicine ,Intellectual Disability ,Genetics ,Animals ,Humans ,Genetics(clinical) ,Cloning, Molecular ,Child ,Gene ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,biology ,Homozygote ,Exons ,Methyltransferases ,Middle Aged ,biology.organism_classification ,Pedigree ,Phenotype ,Codon, Nonsense ,RNA splicing ,Drosophila ,Female ,Drosophila melanogaster ,030217 neurology & neurosurgery - Abstract
With a prevalence between 1 and 3%, hereditary forms of intellectual disability (ID) are among the most important problems in health care. Particularly, autosomal-recessive forms of the disorder have a very heterogeneous molecular basis, and genes with an increased number of disease-causing mutations are not common. Here, we report on three different mutations (two nonsense mutations, c.679C>T [p.Gln227( *)] and c.1114C>T [p.Gln372( *)], as well as one splicing mutation, g.6622224A>C [p.Ile179Argfs( *)192]) that cause a loss of the tRNA-methyltransferase-encoding NSUN2 main transcript in homozygotes. We identified the mutations by sequencing exons and exon-intron boundaries within the genomic region where the linkage intervals of three independent consanguineous families of Iranian and Kurdish origin overlapped with the previously described MRT5 locus. In order to gain further evidence concerning the effect of a loss of NSUN2 on memory and learning, we constructed a Drosophila model by deleting the NSUN2 ortholog, CG6133, and investigated the mutants by using molecular and behavioral approaches. When the Drosophila melanogaster NSUN2 ortholog was deleted, severe short-term-memory (STM) deficits were observed; STM could be rescued by re-expression of the wild-type protein in the nervous system. The humans homozygous for NSUN2 mutations showed an overlapping phenotype consisting of moderate to severe ID and facial dysmorphism (which includes a long face, characteristic eyebrows, a long nose, and a small chin), suggesting that mutations in this gene might even induce a syndromic form of ID. Moreover, our observations from the Drosophila model point toward an evolutionarily conserved role of RNA methylation in normal cognitive development.
- Published
- 2012
26. Fragile X syndrome screening of families with consanguineous and non-consanguineous parents in the Iranian population
- Author
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Kimia Kahrizi, Gholamreza Bahrami Monajemi, Marzieh Mohseni, Seyedeh Sedigheh Abedini, Susan Banihashemi, Hossein Najmabadi, Hossein Darvish, Farkhondeh Behjati, Hans-Hilger Ropers, Alireza Pouya, Lia Abbasi Moheb, Nooshin Nikzat, Sahar Esmaeeli Nieh, and Neda Mansoorian
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Pediatrics ,medicine.medical_specialty ,Offspring ,Population ,Iran ,Iranian population ,Consanguinity ,Gene Frequency ,Genes, X-Linked ,Intellectual Disability ,Genetics ,medicine ,Humans ,In patient ,Family ,Genetic Testing ,education ,Genetics (clinical) ,education.field_of_study ,business.industry ,General Medicine ,medicine.disease ,FMR1 ,Developmental disorder ,Fragile X syndrome ,Fragile X Syndrome ,Female ,business ,Consanguineous Marriage - Abstract
Fragile X syndrome is the most common form of inherited mental retardation (MR). It is caused by the expansion of CGG triplet repeats in the fragile X mental retardation 1 (FMR1) gene. In mentally retarded males, the frequency of fragile X syndrome is approximately 2-3 percent, but little is known about its proportion in mentally retarded patients from countries where parental consanguinity is common. The objective of this study was to estimate the frequency of fragile X syndrome (FXS) in mentally retarded patients from Iran. We examined a total of 508 families with MR that had been referred to the Genetics Research Center (GRC) in Tehran of which 467 families had at least two mentally retarded children. In 384 families, the parents were related and in 124 they were not related of which most of them had putative or established X-linked inheritance pattern. Full FMR1 mutations were found in 32 of the 508 families studied (6.3%), in 19 out of 124 families with apparently unrelated parents (15.3%), and in 13 of the 384 consanguineous families (3.4%). Thus, in Iran, the relative frequency of FXS seems to be high, and in patients with unrelated parents is much higher. We also show that even in families with consanguineous parents, FXS has to be ruled out before assuming that familial MR is due to autosomal recessive gene defects. Molecular studies are in progress to explain the high proportion of FMR1 mutations in mentally retarded offspring of unrelated Iranian parents.
- Published
- 2008
27. SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly
- Author
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Christian Becker, Hossein Najmabadi, Reinhard Ullmann, Steffen Lenzner, Peter Nürnberg, Sahar Esmaeeli Nieh, Masoud Garshasbi, Reza Vazifehmand, Hans-Hilger Ropers, Seyedeh Sedigheh Abedini, Farkhondeh Behjati, M. Mahdi Motazacker, Andreas W. Kuss, Fikret Erdogan, Andreas Tzschach, Kimia Kahrizi, Saghar Ghasemi Firouzabadi, Franz Rüschendorf, and Experimental Vascular Medicine
- Subjects
Adult ,Male ,Microcephaly ,Adolescent ,Single-nucleotide polymorphism ,Cell Cycle Proteins ,Genes, Recessive ,Nerve Tissue Proteins ,Consanguinity ,Biology ,Polymorphism, Single Nucleotide ,Gene mapping ,Intellectual Disability ,Genetics ,medicine ,Humans ,Family ,Genetics (clinical) ,Autosome ,Homozygote ,Chromosome Mapping ,Disease gene identification ,medicine.disease ,Microarray Analysis ,Pedigree ,Cytoskeletal Proteins ,Female ,Gene Deletion ,Mild microcephaly ,SNP array - Abstract
Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based homozygosity mapping and high-resolution microarray-based comparative genomic hybridization (array CGH) revealed a deletion of approximately 150-200 kb, encompassing the promoter and the first six exons of the MCPH1 gene, one out of four genes that have been previously implicated in ARMR with microcephaly. Reexamination of affected individuals revealed a high proportion of prematurely condensed chromosomes, which is a hallmark of this condition, but in spite of the severity of the mutation, all patients showed only borderline to mild microcephaly. Therefore the phenotypic spectrum of MCPH1 mutations may be wider than previously assumed, with ARMR being the only consistent clinical finding.
- Published
- 2005
28. Both Rare and De Novo Copy Number Variants Are Prevalent in Agenesis of the Corpus Callosum but Not in Cerebellar Hypoplasia or Polymicrogyria
- Author
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Sajan, Samin A., primary, Fernandez, Liliana, additional, Nieh, Sahar Esmaeeli, additional, Rider, Eric, additional, Bukshpun, Polina, additional, Wakahiro, Mari, additional, Christian, Susan L., additional, Rivière, Jean-Baptiste, additional, Sullivan, Christopher T., additional, Sudi, Jyotsna, additional, Herriges, Michael J., additional, Paciorkowski, Alexander R., additional, Barkovich, A. James, additional, Glessner, Joseph T., additional, Millen, Kathleen J., additional, Hakonarson, Hakon, additional, Dobyns, William B., additional, and Sherr, Elliott H., additional
- Published
- 2013
- Full Text
- View/download PDF
29. A Defect in the Ionotropic Glutamate Receptor 6 Gene ( GRIK2) Is Associated with Autosomal Recessive Mental Retardation
- Author
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Motazacker, Mohammad Mahdi, Rost, Benjamin Rainer, Hucho, Tim, Garshasbi, Masoud, Kahrizi, Kimia, Ullmann, Reinhard, Abedini, Seyedeh Sedigheh, Nieh, Sahar Esmaeeli, Amini, Saeid Hosseini, Goswami, Chandan, Tzschach, Andreas, Jensen, Lars Riff, Schmitz, Dietmar, Ropers, Hans Hilger, Najmabadi, Hossein, and Kuss, Andreas Walter
- Published
- 2007
- Full Text
- View/download PDF
30. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci
- Author
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Najmabadi, Hossein, primary, Motazacker, Mohammad Mahdi, additional, Garshasbi, Masoud, additional, Kahrizi, Kimia, additional, Tzschach, Andreas, additional, Chen, Wei, additional, Behjati, Farkhondeh, additional, Hadavi, Valeh, additional, Nieh, Sahar Esmaeeli, additional, Abedini, Seyedeh Sedigheh, additional, Vazifehmand, Reza, additional, Firouzabadi, Saghar Ghasemi, additional, Jamali, Payman, additional, Falah, Masoumeh, additional, Seifati, Seyed Morteza, additional, Grüters, Annette, additional, Lenzner, Steffen, additional, Jensen, Lars R., additional, Rüschendorf, Franz, additional, Kuss, Andreas W., additional, and Ropers, H. Hilger, additional
- Published
- 2006
- Full Text
- View/download PDF
31. SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly
- Author
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Garshasbi, Masoud, primary, Motazacker, Mohammad Mahdi, additional, Kahrizi, Kimia, additional, Behjati, Farkhondeh, additional, Abedini, Seyedeh Sedigheh, additional, Nieh, Sahar Esmaeeli, additional, Firouzabadi, Saghar Ghasemi, additional, Becker, Christian, additional, Rüschendorf, Franz, additional, Nürnberg, Peter, additional, Tzschach, Andreas, additional, Vazifehmand, Reza, additional, Erdogan, Fikret, additional, Ullmann, Reinhard, additional, Lenzner, Steffen, additional, Kuss, Andreas W., additional, Ropers, H. Hilger, additional, and Najmabadi, Hossein, additional
- Published
- 2005
- Full Text
- View/download PDF
32. Both Rare and De Novo Copy Number Variants Are Prevalent in Agenesis of the Corpus Callosum but Not in Cerebellar Hypoplasia or Polymicrogyria.
- Author
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Sajan, Samin A., Fernandez, Liliana, Nieh, Sahar Esmaeeli, Rider, Eric, Bukshpun, Polina, Wakahiro, Mari, Christian, Susan L., Rivière, Jean-Baptiste, Sullivan, Christopher T., Sudi, Jyotsna, Herriges, Michael J., Paciorkowski, Alexander R., Barkovich, A. James, Glessner, Joseph T., Millen, Kathleen J., Hakonarson, Hakon, Dobyns, William B., and Sherr, Elliott H.
- Subjects
AGENESIS of corpus callosum ,BRAIN abnormalities ,DISEASE prevalence ,DNA copy number variations ,KARYOTYPES - Abstract
Agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and polymicrogyria (PMG) are severe congenital brain malformations with largely undiscovered causes. We conducted a large-scale chromosomal copy number variation (CNV) discovery effort in 255 ACC, 220 CBLH, and 147 PMG patients, and 2,349 controls. Compared to controls, significantly more ACC, but unexpectedly not CBLH or PMG patients, had rare genic CNVs over one megabase (p = 1.48×10
−3 ; odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.89–5.39). Rare genic CNVs were those that impacted at least one gene in less than 1% of the combined population of patients and controls. Compared to controls, significantly more ACC but not CBLH or PMG patients had rare CNVs impacting over 20 genes (p = 0.01; OR = 2.95; 95% CI = 1.69–5.18). Independent qPCR confirmation showed that 9.4% of ACC patients had de novo CNVs. These, in comparison to inherited CNVs, preferentially overlapped de novo CNVs previously observed in patients with autism spectrum disorders (p = 3.06×10−4 ; OR = 7.55; 95% CI = 2.40–23.72). Interestingly, numerous reports have shown a reduced corpus callosum area in autistic patients, and diminished social and executive function in many ACC patients. We also confirmed and refined previously known CNVs, including significantly narrowing the 8p23.1-p11.1 duplication present in 2% of our current ACC cohort. We found six novel CNVs, each in a single patient, that are likely deleterious: deletions of 1p31.3-p31.1, 1q31.2-q31.3, 5q23.1, and 15q11.2-q13.1; and duplications of 2q11.2-q13 and 11p14.3-p14.2. One ACC patient with microcephaly had a paternally inherited deletion of 16p13.11 that included NDE1. Exome sequencing identified a recessive maternally inherited nonsense mutation in the non-deleted allele of NDE1, revealing the complexity of ACC genetics. This is the first systematic study of CNVs in congenital brain malformations, and shows a much higher prevalence of large gene-rich CNVs in ACC than in CBLH and PMG. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
33. SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly.
- Author
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Masoud Garshasbi, Motazacker, Mohammad Mahdi, Kahrizi, Kimia, Behjati, Farkhondeh, Abedini, Seyedeh Sedigheh, Nieh, Sahar Esmaeeli, Firouzabadi, Saghar Ghasemi, Becker, Christian, Rüschendorf, Franz, Nürnberg, Peter, Tzschach, Andreas, Vazifehmand, Reza, Erdogan, Fikret, Ullmann, Reinhard, Lenzner, Steffen, Kuss, Andreas W., Ropers, H. Hilger, and Najmabadi, Hossein
- Subjects
INTELLECTUAL disabilities ,PATIENTS ,EXONS (Genetics) ,SPLIT genes ,PROMOTERS (Genetics) ,GENES ,CHROMOSOMES ,GENETIC mutation ,GENETIC research ,HUMAN genetics - Abstract
Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based homozygosity mapping and high-resolution microarray-based comparative genomic hybridization (array CGH) revealed a deletion of approximately 150–200 kb, encompassing the promoter and the first six exons of the MCPH1 gene, one out of four genes that have been previously implicated in ARMR with microcephaly. Reexamination of affected individuals revealed a high proportion of prematurely condensed chromosomes, which is a hallmark of this condition, but in spite of the severity of the mutation, all patients showed only borderline to mild microcephaly. Therefore the phenotypic spectrum of MCPH1 mutations may be wider than previously assumed, with ARMR being the only consistent clinical finding. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
34. Epileptic encephalopathies: new genes and new pathways.
- Author
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Nieh SE and Sherr EH
- Subjects
- Epilepsies, Myoclonic diagnosis, Epilepsies, Myoclonic genetics, Epilepsies, Myoclonic therapy, Epilepsy diagnosis, Epilepsy therapy, Humans, Infant, Infant, Newborn, Landau-Kleffner Syndrome diagnosis, Landau-Kleffner Syndrome genetics, Landau-Kleffner Syndrome therapy, Lennox Gastaut Syndrome diagnosis, Lennox Gastaut Syndrome genetics, Lennox Gastaut Syndrome therapy, Sequence Analysis, DNA, Spasms, Infantile diagnosis, Spasms, Infantile genetics, Spasms, Infantile therapy, Brain physiopathology, Epilepsy genetics
- Abstract
Epileptic encephalopathies represent a group of devastating epileptic disorders that occur early in life and are often characterized by pharmaco-resistant epilepsy, persistent severe electroencephalographic abnormalities, and cognitive dysfunction or decline. Next generation sequencing technologies have increased the speed of gene discovery tremendously. Whereas ion channel genes were long considered to be the only significant group of genes implicated in the genetic epilepsies, a growing number of non-ion-channel genes are now being identified. As a subgroup of the genetically mediated epilepsies, epileptic encephalopathies are complex and heterogeneous disorders, making diagnosis and treatment decisions difficult. Recent exome sequencing data suggest that mutations causing epileptic encephalopathies are often sporadic, typically resulting from de novo dominant mutations in a single autosomal gene, although inherited autosomal recessive and X-linked forms also exist. In this review we provide a summary of the key features of several early- and mid-childhood onset epileptic encephalopathies including Ohtahara syndrome, Dravet syndrome, Infantile spasms and Lennox Gastaut syndrome. We review the recent next generation sequencing findings that may impact treatment choices. We also describe the use of conventional and newer anti-epileptic and hormonal medications in the various syndromes based on their genetic profile. At a biological level, developments in cellular reprogramming and genome editing represent a new direction in modeling these pediatric epilepsies and could be used in the development of novel and repurposed therapies.
- Published
- 2014
- Full Text
- View/download PDF
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