43 results on '"Rieubland, Claudine"'
Search Results
2. Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders
- Author
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Gracia-Diaz, Carolina, Zhou, Yijing, Yang, Qian, Maroofian, Reza, Espana-Bonilla, Paula, Lee, Chul-Hwan, Zhang, Shuo, Padilla, Natàlia, Fueyo, Raquel, Waxman, Elisa A., Lei, Sunyimeng, Otrimski, Garrett, Li, Dong, Sheppard, Sarah E., Mark, Paul, Harr, Margaret H., Hakonarson, Hakon, Rodan, Lance, Jackson, Adam, Vasudevan, Pradeep, Powel, Corrina, Mohammed, Shehla, Maddirevula, Sateesh, Alzaidan, Hamad, Faqeih, Eissa A., Efthymiou, Stephanie, Turchetti, Valentina, Rahman, Fatima, Maqbool, Shazia, Salpietro, Vincenzo, Ibrahim, Shahnaz H., di Rosa, Gabriella, Houlden, Henry, Alharbi, Maha Nasser, Al-Sannaa, Nouriya Abbas, Bauer, Peter, Zifarelli, Giovanni, Estaras, Conchi, Hurst, Anna C. E., Thompson, Michelle L., Chassevent, Anna, Smith-Hicks, Constance L., de la Cruz, Xavier, Holtz, Alexander M., Elloumi, Houda Zghal, Hajianpour, M J, Rieubland, Claudine, Braun, Dominique, Banka, Siddharth, French, Deborah L., Heller, Elizabeth A., Saade, Murielle, Song, Hongjun, Ming, Guo-li, Alkuraya, Fowzan S., Agrawal, Pankaj B., Reinberg, Danny, Bhoj, Elizabeth J., Martínez-Balbás, Marian A., and Akizu, Naiara
- Published
- 2023
- Full Text
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3. Correction: Clinical and genetic analysis further delineates the phenotypic spectrum of ALDH1A3-related anophthalmia and microphthalmia
- Author
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Kesim, Yesim, Ceroni, Fabiola, Damián, Alejandra, Blanco-Kelly, Fiona, Ayuso, Carmen, Williamson, Kathy, Paquis-Flucklinger, Véronique, Bax, Dorine A, Plaisancié, Julie, Rieubland, Claudine, Chamlal, Mostafa, Cortón, Marta, Chassaing, Nicolas, Calvas, Patrick, and Ragge, Nicola K
- Published
- 2023
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4. Clinical delineation, sex differences, and genotype–phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2
- Author
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Faundes, Víctor, Goh, Stephanie, Akilapa, Rhoda, Bezuidenhout, Heidre, Bjornsson, Hans T., Bradley, Lisa, Brady, Angela F., Brischoux-Boucher, Elise, Brunner, Han, Bulk, Saskia, Canham, Natalie, Cody, Declan, Dentici, Maria Lisa, Digilio, Maria Cristina, Elmslie, Frances, Fry, Andrew E., Gill, Harinder, Hurst, Jane, Johnson, Diana, Julia, Sophie, Lachlan, Katherine, Lebel, Robert Roger, Byler, Melissa, Gershon, Eric, Lemire, Edmond, Gnazzo, Maria, Lepri, Francesca Romana, Marchese, Antonia, McEntagart, Meriel, McGaughran, Julie, Mizuno, Seiji, Okamoto, Nobuhiko, Rieubland, Claudine, Rodgers, Jonathan, Sasaki, Erina, Scalais, Emmanuel, Scurr, Ingrid, Suri, Mohnish, van der Burgt, Ineke, Matsumoto, Naomichi, Miyake, Noriko, Benoit, Valérie, Lederer, Damien, and Banka, Siddharth
- Published
- 2021
- Full Text
- View/download PDF
5. Enhancing fetal outcomes in GCK-MODY pregnancies: a precision medicine approach via non-invasive prenatal GCK mutation detection.
- Author
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Schwitzgebel, Valérie M., Blouin, Jean-Louis, Dehos, Barbara, Köhler-Ballan, Bettina, Puder, Jardena J., Rieubland, Claudine, Triantafyllidou, Maria, Zanchi, Anne, Abramowicz, Marc, and Nouspikel, Thierry
- Published
- 2024
- Full Text
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6. Expanding Genotype/Phenotype Correlation in 2p11.2-p12 Microdeletion Syndrome.
- Author
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Ferrario, Alessandra, Aliu, Nijas, Rieubland, Claudine, Vuilleumier, Sébastian, Grabe, Hilary M., and Escher, Pascal
- Subjects
COMPARATIVE genomic hybridization ,AGENESIS of corpus callosum ,PHENOTYPES ,PSYCHOMOTOR disorders ,ARNOLD-Chiari deformity ,GENOTYPES ,INNER ear - Abstract
Chromosomal abnormalities on the short arm of chromosome 2 in the region p11.2 have been associated with developmental delay, intellectual disability, facial anomalies, abnormal ears, skeletal and genital malformations. Here we describe a patient with a de novo interstitial heterozygous microdeletion on the short arm of chromosome 2 in the region p11.2-p12. He presents with facial dysmorphism characterized by a broad and low root of the nose and low-set protruding ears. Clinical examinations during follow-up visits revealed congenital pendular nystagmus, decreased visual acuity and psychomotor development disorder including intellectual disability. The heterozygous 5 Mb-microdeletion was characterized by an array CGH (Comparative Genomic Hybridization) analysis. In the past two decades, nine patients with microdeletions in this region have been identified by array CGH analysis and were reported in the literature. All these patients show psychomotor development disorder and outer and/or inner ear anomalies. In addition, most of the patients have mild to severe intellectual disability and show facial malformations. We reviewed the literature on PubMed and OMIM using the gene/loci names as search terms in an attempt to identify correlations between genes located within the heterozygous microdeletion and the clinical phenotype of the patient, in order to define a recognizable phenotype for the 2p11.2p12 microdeletion syndrome. We discuss additional symptoms that are not systematically present in all patients and contribute to a heterogeneous clinical presentation of this microdeletion syndrome. [ABSTRACT FROM AUTHOR]
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- 2023
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7. The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders
- Author
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Saffari, Afshin, primary, Lau, Tracy, additional, Tajsharghi, Homa, additional, Karimiani, Ehsan Ghayoor, additional, Kariminejad, Ariana, additional, Efthymiou, Stephanie, additional, Zifarelli, Giovanni, additional, Sultan, Tipu, additional, Toosi, Mehran Beiraghi, additional, Sedighzadeh, Sahar, additional, Siu, Victoria Mok, additional, Ortigoza-Escobar, Juan Darío, additional, AlShamsi, Aisha M, additional, Ibrahim, Shahnaz, additional, Al-Sannaa, Nouriya Abbas, additional, Al-Hertani, Walla, additional, Sandra, Whalen, additional, Tarnopolsky, Mark, additional, Alavi, Shahryar, additional, Li, Chumei, additional, Day-Salvatore, Debra-Lynn, additional, Martínez-González, Maria Jesús, additional, Levandoski, Kristin M, additional, Bedoukian, Emma, additional, Madan-Khetarpal, Suneeta, additional, Idleburg, Michaela J, additional, Menezes, Minal Juliet, additional, Siddharth, Aishwarya, additional, Platzer, Konrad, additional, Oppermann, Henry, additional, Smitka, Martin, additional, Collins, Felicity, additional, Lek, Monkol, additional, Shahrooei, Mohmmad, additional, Ghavideldarestani, Maryam, additional, Herman, Isabella, additional, Rendu, John, additional, Faure, Julien, additional, Baker, Janice, additional, Bhambhani, Vikas, additional, Calderwood, Laurel, additional, Akhondian, Javad, additional, Imannezhad, Shima, additional, Mirzadeh, Hanieh Sadat, additional, Hashemi, Narges, additional, Doosti, Mohammad, additional, Safi, Mojtaba, additional, Ahangari, Najmeh, additional, Torbati, Paria Najarzadeh, additional, Abedini, Soheila, additional, Salpietro, Vincenzo, additional, Gulec, Elif Yilmaz, additional, Eshaghian, Safieh, additional, Ghazavi, Mohammadreza, additional, Pascher, Michael T, additional, Vogel, Marina, additional, Abicht, Angela, additional, Moutton, Sébastien, additional, Bruel, Ange-Line, additional, Rieubland, Claudine, additional, Gallati, Sabina, additional, Strom, Tim M, additional, Lochmüller, Hanns, additional, Mohammadi, Mohammad Hasan, additional, Alvi, Javeria Raza, additional, Zackai, Elaine H, additional, Keena, Beth A, additional, Skraban, Cara M, additional, Berger, Seth I, additional, Andrew, Erin H, additional, Rahimian, Elham, additional, Morrow, Michelle M, additional, Wentzensen, Ingrid M, additional, Millan, Francisca, additional, Henderson, Lindsay B, additional, Dafsari, Hormos Salimi, additional, Jungbluth, Heinz, additional, Gomez-Ospina, Natalia, additional, McRae, Anne, additional, Peter, Merlene, additional, Veltra, Danai, additional, Marinakis, Nikolaos M, additional, Sofocleous, Christalena, additional, Ashrafzadeh, Farah, additional, Pehlivan, Davut, additional, Lemke, Johannes R, additional, Melki, Judith, additional, Benezit, Audrey, additional, Bauer, Peter, additional, Weis, Denisa, additional, Lupski, James R, additional, Senderek, Jan, additional, Christodoulou, John, additional, Chung, Wendy K, additional, Goodchild, Rose, additional, Offiah, Amaka C, additional, Moreno-De-Luca, Andres, additional, Suri, Mohnish, additional, Ebrahimi-Fakhari, Darius, additional, Houlden, Henry, additional, and Maroofian, Reza, additional
- Published
- 2023
- Full Text
- View/download PDF
8. Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders
- Author
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National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), University of Alabama at Birmingham, Ministerio de Ciencia e Innovación (España), Ministerio de Educación y Ciencia (España), Manchester Biomedical Research Centre, European Commission, National Institute for Health Research (UK), Wellcome Trust, Cancer Research UK, Medical Research Council (UK), Wellcome Sanger Institute, Gracia-Díaz, Carolina, Zhou, Yijing, Yang, Qian, Maroofian, Reza, España-Bonilla, Paula, Lee, Chul-Hwan, Zhang, Shuo, Padilla, Natàlia, Fueyo, Raquel, Waxman, Elisa A., Lei, Sunyimeng, Otrimski, Garrett, Li, Dong, Sheppard, Sarah E., Mark, Paul, Harr, Margaret H., Hakonarson, Hakon, Rodan, Lance, Jackson, Adam, Vasudevan, Pradeep, Powel, Corrina, Mohammed, Shehla, Maddirevula, Sateesh, Alzaidan, Hamad, Faqeih, Eissa A., Efthymiou, Stephanie, Turchetti, Valentina, Rahman, Fátima, Maqbool, Shazia, Salpietro, Vincenzo, Ibrahim, Shahnaz H., di Rosa, Gabriella, Houlden, Henry, Alharbi, Maha Nasser, Al-Sannaa, Nouriya Abbas, Bauer, Peter, Zifarelli, Giovanni, Estaras, Conchi, Hurst, Anna C. E., Thompson, Michelle L., Chassevent, Anna, Smith-Hicks, Constance L., Cruz, Xavier de la, Holtz, Alexander M., Elloumi, Houda Zghal, Hajianpour, M. J., Rieubland, Claudine, Braun, Dominique, Banka, Siddharth, French, Deborah L., Heller, Elizabeth A., Saade, Murielle, Song, Hongjun, Ming, Guo-Li, Alkuraya, Fowzan S., Agrawal, Pankaj B., Reinberg, Danny, Bhoj, Elizabeth J., Martínez-Balbás, Marian, Akizu, Naiara, National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), University of Alabama at Birmingham, Ministerio de Ciencia e Innovación (España), Ministerio de Educación y Ciencia (España), Manchester Biomedical Research Centre, European Commission, National Institute for Health Research (UK), Wellcome Trust, Cancer Research UK, Medical Research Council (UK), Wellcome Sanger Institute, Gracia-Díaz, Carolina, Zhou, Yijing, Yang, Qian, Maroofian, Reza, España-Bonilla, Paula, Lee, Chul-Hwan, Zhang, Shuo, Padilla, Natàlia, Fueyo, Raquel, Waxman, Elisa A., Lei, Sunyimeng, Otrimski, Garrett, Li, Dong, Sheppard, Sarah E., Mark, Paul, Harr, Margaret H., Hakonarson, Hakon, Rodan, Lance, Jackson, Adam, Vasudevan, Pradeep, Powel, Corrina, Mohammed, Shehla, Maddirevula, Sateesh, Alzaidan, Hamad, Faqeih, Eissa A., Efthymiou, Stephanie, Turchetti, Valentina, Rahman, Fátima, Maqbool, Shazia, Salpietro, Vincenzo, Ibrahim, Shahnaz H., di Rosa, Gabriella, Houlden, Henry, Alharbi, Maha Nasser, Al-Sannaa, Nouriya Abbas, Bauer, Peter, Zifarelli, Giovanni, Estaras, Conchi, Hurst, Anna C. E., Thompson, Michelle L., Chassevent, Anna, Smith-Hicks, Constance L., Cruz, Xavier de la, Holtz, Alexander M., Elloumi, Houda Zghal, Hajianpour, M. J., Rieubland, Claudine, Braun, Dominique, Banka, Siddharth, French, Deborah L., Heller, Elizabeth A., Saade, Murielle, Song, Hongjun, Ming, Guo-Li, Alkuraya, Fowzan S., Agrawal, Pankaj B., Reinberg, Danny, Bhoj, Elizabeth J., Martínez-Balbás, Marian, and Akizu, Naiara
- Abstract
Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders.
- Published
- 2023
9. Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome
- Author
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Maas, Saskia M., Shaw, Adam C., Bikker, Hennie, Lüdecke, Hermann-Josef, van der Tuin, Karin, Badura-Stronka, Magdalena, Belligni, Elga, Biamino, Elisa, Bonati, Maria Teresa, Carvalho, Daniel R., Cobben, JanMaarten, de Man, Stella A., Den Hollander, Nicolette S., Di Donato, Nataliya, Garavelli, Livia, Grønborg, Sabine, Herkert, Johanna C., Hoogeboom, A. Jeannette M., Jamsheer, Aleksander, Latos-Bielenska, Anna, Maat-Kievit, Anneke, Magnani, Cinzia, Marcelis, Carlo, Mathijssen, Inge B., Nielsen, Maartje, Otten, Ellen, Ousager, Lilian B., Pilch, Jacek, Plomp, Astrid, Poke, Gemma, Poluha, Anna, Posmyk, Renata, Rieubland, Claudine, Silengo, Margharita, Simon, Marleen, Steichen, Elisabeth, Stumpel, Connie, Szakszon, Katalin, Polonkai, Edit, van den Ende, Jenneke, van der Steen, Antony, van Essen, Ton, van Haeringen, Arie, van Hagen, Johanna M., Verheij, Joke B.G.M., Mannens, Marcel M., and Hennekam, Raoul C.
- Published
- 2015
- Full Text
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10. Compound-heterozygous GRIN2A null variants associated with severe developmental and epileptic encephalopathy
- Author
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Strehlow, Vincent, Rieubland, Claudine, Gallati, Sabrina, Kim, Sukhan, Myers, Scott J, Peterson, Vincent, Ramsey, Amy J, Teuscher, Daniel D, Traynelis, Stephen F, and Lemke, Johannes R
- Subjects
Mice ,Phenotype ,Neurology ,Mental Disorders ,Animals ,Humans ,Epilepsy, Generalized ,Female ,Neurology (clinical) ,610 Medizin und Gesundheit ,Child ,Receptors, N-Methyl-D-Aspartate - Abstract
We report on an 8-year-old girl with severe developmental and epileptic encephalopathy due to the compound heterozygous null variants p.(Gln661*) and p.(Leu830Profs*2) in GRIN2A resulting in a knockout of the human GluN2A subunit of the N-methyl-D-aspartate receptor. Both parents had less severe GRIN2A-related phenotypes and were heterozygous carriers of the respective null variant. Functional investigations of both variants suggested a loss-of-function effect. This is the first description of an autosomal recessive, biallelic type of GRIN2A-related disorder. Nonetheless, there are marked parallels to two previously published families with severe epileptic encephalopathy due to homozygous null variants in GRIN1 as well as various knockout animal models. Compared to heterozygous null variants, biallelic knockout of either GluN1 or GluN2A is associated with markedly more severe phenotypes in both humans and mice. Furthermore, recent findings enable a potential precision medicine approach targeting GRIN-related disorders due to null variants.
- Published
- 2022
11. Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology
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Banka, Siddharth, primary, Bennington, Abigail, additional, Baker, Martin J, additional, Rijckmans, Ellen, additional, Clemente, Giuliana D, additional, Ansor, Nurhuda Mohamad, additional, Sito, Hilary, additional, Prasad, Pritha, additional, Anyane-Yeboa, Kwame, additional, Badalato, Lauren, additional, Dimitrov, Boyan, additional, Fitzpatrick, David, additional, Hurst, Anna C E, additional, Jansen, Anna C, additional, Kelly, Melissa A, additional, Krantz, Ian, additional, Rieubland, Claudine, additional, Ross, Meredith, additional, Rudy, Natasha L, additional, Sanz, Javier, additional, Stouffs, Katrien, additional, Xu, Zhuo Luan, additional, Malliri, Angeliki, additional, Kazanietz, Marcelo G, additional, and Millard, Tom H, additional
- Published
- 2022
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12. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy
- Author
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Reinthaler, Eva M., Lal, Dennis, Lebon, Sebastien, Hildebrand, Michael S., Dahl, Hans-Henrik M., Regan, Brigid M., Feucht, Martha, Steinböck, Hannelore, Neophytou, Birgit, Ronen, Gabriel M., Roche, Laurian, Gruber-Sedlmayr, Ursula, Geldner, Julia, Haberlandt, Edda, Hoffmann, Per, Herms, Stefan, Gieger, Christian, Waldenberger, Melanie, Franke, Andre, Wittig, Michael, Schoch, Susanne, Becker, Albert J., Hahn, Andreas, Männik, Katrin, Toliat, Mohammad R., Winterer, Georg, Lerche, Holger, Nürnberg, Peter, Mefford, Heather, Scheffer, Ingrid E., Berkovic, Samuel F., Beckmann, Jacques S., Sander, Thomas, Jacquemont, Sebastien, Reymond, Alexandre, Zimprich, Fritz, Neubauer, Bernd A., Reinthaler, Eva M., Zimprich, Fritz, Feucht, Martha, Steinböck, Hannelore, Neophytou, Birgit, Geldner, Julia, Gruber-Sedlmayr, Ursula, Haberlandt, Edda, Ronen, Gabriel M., Roche, Laurian, Lal, Dennis, Nürnberg, Peter, Sander, Thomas, Lerche, Holger, Neubauer, Bernd, Zimprich, Fritz, Mörzinger, Martina, Feucht, Martha, Suls, Arvid, Weckhuysen, Sarah, Claes, Lieve, Deprez, Liesbet, Smets, Katrien, Van Dyck, Tine, Deconinck, Tine, De Jonghe, Peter, Møller, Rikke S, Klitten, Laura L., Hjalgrim, Helle, Møller, Rikke S, Campus, Kiel, Helbig, Ingo, Muhle, Hiltrud, Ostertag, Philipp, von Spiczak, Sarah, Stephani, Ulrich, Nürnberg, Peter, Sander, Thomas, Trucks, Holger, Elger, Christian E., Kleefu-Lie, Ailing A., Kunz, Wolfram S., Surges, Rainer, Gaus, Verena, Janz, Dieter, Sander, Thomas, Schmitz, Bettina, Rosenow, Felix, Klein, Karl Martin, Reif, Philipp S., Oertel, Wolfgang H., Hamer, Hajo M., Becker, Felicitas, Weber, Yvonne, Lerche, Holger, Koeleman, Bobby P.C., de Kovel, Carolien, Lindhout, Dick, Lindhout, Dick, Ameil, Agnès, Andrieux, Joris, Bouquillon, Sonia, Boute, Odile, de Flandre, Jeanne, Cuisset, Jean Marie, Cuvellier, Jean-Christophe, Salengro, Roger, David, Albert, de Vries, Bert, Delrue, Marie-Ange, Doco-Fenzy, Martine, Fernandez, Bridget A., Heron, Delphine, Keren, Boris, Lebel, Robert, Leheup, Bruno, Lewis, Suzanne, Mencarelli, Maria Antonietta, Mignot, Cyril, Minet, Jean-Claude, Moerman, Alexandre, Morice-Picard, Fanny, Mucciolo, Mafalda, Ounap, Katrin, Pasquier, Laurent, Petit, Florence, Ragona, Francesca, Rajcan-Separovic, Evica, Renieri, Alessandra, Rieubland, Claudine, Sanlaville, Damien, Sarrazin, Elisabeth, Shen, Yiping, van Haelst, Mieke, and Silfhout, Anneke Vulto-van
- Published
- 2014
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13. Delineation of phenotypes and genotypes related to cohesin structural protein RAD21
- Author
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Krab, Lianne C., Marcos-Alcalde, Iñigo, Assaf, Melissa, Balasubramanian, Meena, Bayer Andersen, Janne, Bisgaard, Anne-Marie, Fitzpatrick, David R., Gudmundsson, Sanna, Huisman, Sylvia A., Kalayci, Tugba, Maas, Saskia M., Martinez, Francisco, McKee, Shane, Menke, Leonie A., Mulder, Paul A., Murch, Oliver D., Parker, Michael, Pie, Juan, Ramos, Feliciano J., Rieubland, Claudine, Mokry, Jill A. Rosenfeld, Scarano, Emanuela, Shinawi, Marwan, Gomez-Puertas, Paulino, Tümer, Zeynep, Hennekam, Raoul C., Krab, Lianne C., Marcos-Alcalde, Iñigo, Assaf, Melissa, Balasubramanian, Meena, Bayer Andersen, Janne, Bisgaard, Anne-Marie, Fitzpatrick, David R., Gudmundsson, Sanna, Huisman, Sylvia A., Kalayci, Tugba, Maas, Saskia M., Martinez, Francisco, McKee, Shane, Menke, Leonie A., Mulder, Paul A., Murch, Oliver D., Parker, Michael, Pie, Juan, Ramos, Feliciano J., Rieubland, Claudine, Mokry, Jill A. Rosenfeld, Scarano, Emanuela, Shinawi, Marwan, Gomez-Puertas, Paulino, Tümer, Zeynep, and Hennekam, Raoul C.
- Abstract
RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype–phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in NIPBL or SMC1A for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the RAD21 variant is uncertain. Variants were frequently familial, and genotype–phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a RAD21 variation.
- Published
- 2020
- Full Text
- View/download PDF
14. Delineation of phenotypes and genotypes related to cohesin structural protein RAD21
- Author
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Ministerio de Ciencia, Innovación y Universidades (España), Krabbe, Lianne C., Marcos-Alcalde, Íñigo, Assafin, Melissa, Balasubramanian, Meena, Andersen, Janne B., Bisgaard, Anne‑Marie, Fitzpatrick, David R., Gudmundsson, Sanna, Huisman, Sylvia A., Kalayci, Tugba, Maas, Saskia M., Martínez, Francisco, Mckee, Shane, Menke, Leonie A., Mulder, Paul A., Murch, Oliver D., Parker, Michael, Pie, Juan, Ramos, Feliciano J., Rieubland, Claudine, Rosenfeld Mokry, Jill A., Scarano, Emanuela, Shinawi, Marwan, Gómez-Puertas, Paulino, Tümer, Zeynep, Hennekam, Raoul C., Ministerio de Ciencia, Innovación y Universidades (España), Krabbe, Lianne C., Marcos-Alcalde, Íñigo, Assafin, Melissa, Balasubramanian, Meena, Andersen, Janne B., Bisgaard, Anne‑Marie, Fitzpatrick, David R., Gudmundsson, Sanna, Huisman, Sylvia A., Kalayci, Tugba, Maas, Saskia M., Martínez, Francisco, Mckee, Shane, Menke, Leonie A., Mulder, Paul A., Murch, Oliver D., Parker, Michael, Pie, Juan, Ramos, Feliciano J., Rieubland, Claudine, Rosenfeld Mokry, Jill A., Scarano, Emanuela, Shinawi, Marwan, Gómez-Puertas, Paulino, Tümer, Zeynep, and Hennekam, Raoul C.
- Abstract
RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype–phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in NIPBL or SMC1A for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the RAD21 variant is uncertain. Variants were frequently familial, and genotype–phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a RAD21 variation.
- Published
- 2020
15. Duplication of the sodium channel gene cluster on 2q24 in children with early onset epilepsy
- Author
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Goeggel Simonetti, Barbara, Rieubland, Claudine, Courage, Carolina, Strozzi, Susi, Tschumi, Sibylle, Gallati, Sabina, and Lemke, Johannes R.
- Published
- 2012
- Full Text
- View/download PDF
16. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus
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Jacquemont, Sébastien, Reymond, Alexandre, Zufferey, Flore, Harewood, Louise, Walters, Robin G., Kutalik, Zoltán, Martinet, Danielle, Shen, Yiping, Valsesia, Armand, Beckmann, Noam D., Thorleifsson, Gudmar, Belfiore, Marco, Bouquillon, Sonia, Campion, Dominique, de Leeuw, Nicole, de Vries, Bert B. A., Esko, Tõnu, Fernandez, Bridget A., Fernández-Aranda, Fernando, Fernández-Real, José Manuel, Gratacòs, Mònica, Guilmatre, Audrey, Hoyer, Juliane, Jarvelin, Marjo-Riitta, Kooy, Frank R., Kurg, Ants, Le Caignec, Cédric, Männik, Katrin, Platt, Orah S., Sanlaville, Damien, Van Haelst, Mieke M., Gomez, Sergi Villatoro, Walha, Faida, Wu, Bai-lin, Yu, Yongguo, Aboura, Azzedine, Addor, Marie-Claude, Alembik, Yves, Antonarakis, Stylianos E., Arveiler, Benoît, Barth, Magalie, Bednarek, Nathalie, Béna, Frédérique, Bergmann, Sven, Beri, Mylène, Bernardini, Laura, Blaumeiser, Bettina, Bonneau, Dominique, Bottani, Armand, Boute, Odile, Brunner, Han G., Cailley, Dorothée, Callier, Patrick, Chiesa, Jean, Chrast, Jacqueline, Coin, Lachlan, Coutton, Charles, Cuisset, Jean-Marie, Cuvellier, Jean-Christophe, David, Albert, de Freminville, Bénédicte, Delobel, Bruno, Delrue, Marie-Ange, Demeer, Bénédicte, Descamps, Dominique, Didelot, Gérard, Dieterich, Klaus, Disciglio, Vittoria, Doco-Fenzy, Martine, Drunat, Séverine, Duban-Bedu, Bénédicte, Dubourg, Christèle, Moustafa, Julia S. El-Sayed, Elliott, Paul, Faas, Brigitte H. W., Faivre, Laurence, Faudet, Anne, Fellmann, Florence, Ferrarini, Alessandra, Fisher, Richard, Flori, Elisabeth, Forer, Lukas, Gaillard, Dominique, Gerard, Marion, Gieger, Christian, Gimelli, Stefania, Gimelli, Giorgio, Grabe, Hans J., Guichet, Agnès, Guillin, Olivier, Hartikainen, Anna-Liisa, Heron, Délphine, Hippolyte, Loyse, Holder, Muriel, Homuth, Georg, Isidor, Bertrand, Jaillard, Sylvie, Jaros, Zdenek, Jiménez-Murcia, Susana, Helas, Géraldine Joly, Jonveaux, Philippe, Kaksonen, Satu, Keren, Boris, Kloss-Brandstätter, Anita, Knoers, Nine V. A. M., Koolen, David A., Kroisel, Peter M., Kronenberg, Florian, Labalme, Audrey, Landais, Emilie, Lapi, Elisabetta, Layet, Valérie, Legallic, Solenn, Leheup, Bruno, Leube, Barbara, Lewis, Suzanne, Lucas, Josette, MacDermot, Kay D., Magnusson, Pall, Marshall, Christian, Mathieu-Dramard, Michèle, McCarthy, Mark I., Meitinger, Thomas, Mencarelli, Maria Antonietta, Merla, Giuseppe, Moerman, Alexandre, Mooser, Vincent, Morice-Picard, Fanny, Mucciolo, Mafalda, Nauck, Matthias, Ndiaye, Ndeye Coumba, Nordgren, Ann, Pasquier, Laurent, Petit, Florence, Pfundt, Rolph, Plessis, Ghislaine, Rajcan-Separovic, Evica, Ramelli, Gian Paolo, Rauch, Anita, Ravazzolo, Roberto, Reis, Andre, Renieri, Alessandra, Richart, Cristobal, Ried, Janina S., Rieubland, Claudine, Roberts, Wendy, Roetzer, Katharina M., Rooryck, Caroline, Rossi, Massimiliano, Saemundsen, Evald, Satre, Véronique, Schurmann, Claudia, Sigurdsson, Engilbert, Stavropoulos, Dimitri J., Stefansson, Hreinn, Tengström, Carola, Thorsteinsdóttir, Unnur, Tinahones, Francisco J., Touraine, Renaud, Vallée, Louis, van Binsbergen, Ellen, Van der Aa, Nathalie, Vincent-Delorme, Catherine, Visvikis-Siest, Sophie, Vollenweider, Peter, Völzke, Henry, Vulto-van Silfhout, Anneke T., Waeber, Gérard, Wallgren-Pettersson, Carina, Witwicki, Robert M., Zwolinksi, Simon, Andrieux, Joris, Estivill, Xavier, Gusella, James F., Gustafsson, Omar, Metspalu, Andres, Scherer, Stephen W., Stefansson, Kari, Blakemore, Alexandra I. F., Beckmann, Jacques S., and Froguel, Philippe
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- 2011
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17. Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice
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Fokstuen, Siv, Munoz, Analia, Melacini, Paola, Iliceto, Sabino, Perrot, Andreas, Özcelik, Cemil, Jeanrenaud, Xavier, Rieubland, Claudine, Farr, Martin, Faber, Lothar, Sigwart, Ulrich, Mach, François, Lerch, René, Antonarakis, Stylianos E, and Blouin, Jean-Louis
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- 2011
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18. Delineation of phenotypes and genotypes related to cohesin structural protein RAD21
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Krab, Lianne C., primary, Marcos-Alcalde, Iñigo, additional, Assaf, Melissa, additional, Balasubramanian, Meena, additional, Andersen, Janne Bayer, additional, Bisgaard, Anne-Marie, additional, Fitzpatrick, David R., additional, Gudmundsson, Sanna, additional, Huisman, Sylvia A., additional, Kalayci, Tugba, additional, Maas, Saskia M., additional, Martinez, Francisco, additional, McKee, Shane, additional, Menke, Leonie A., additional, Mulder, Paul A., additional, Murch, Oliver D., additional, Parker, Michael, additional, Pie, Juan, additional, Ramos, Feliciano J., additional, Rieubland, Claudine, additional, Rosenfeld Mokry, Jill A., additional, Scarano, Emanuela, additional, Shinawi, Marwan, additional, Gómez-Puertas, Paulino, additional, Tümer, Zeynep, additional, and Hennekam, Raoul C., additional
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- 2020
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19. Molecular defects of the C7 gene in two patients with complement C7 deficiency
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Barroso, Sonia, Rieubland, Claudine, JoséÁlvarez, Antonia, López-Trascasa, Margarita, Bart, Pierre-Alexandre, Núñez-Roldán, Antonio, and Sánchez, Berta
- Published
- 2006
20. Functional Consequences of a SDHB Gene Mutation in an Apparently Sporadic Pheochromocytoma
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Gimenez-Roqueplo, Anne-Paule, Favier, Judith, Rustin, Pierre, Rieubland, Claudine, Kerlan, Véronique, Plouin, Pierre-François, Rötig, Agnès, and Jeunemaitre, Xavier
- Published
- 2002
21. Recommendations for genetic testing and counselling after sudden cardiac death: practical aspects for Swiss practice
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Medeiros Domingo, Argelia, Bolliger, Stephan, Gräni, Christoph, Rieubland, Claudine, Hersch, Deborah, Asatryan, Babken, Schyma, Christian, Saguner, Ardan Muammer, Wyler, Daniel, Bhuiyan, Zahir, Fellman, Florence, Osculati, Antonio Marco, Ringger, Rebekka, Fokstuen, Siv, Sabatasso, Sara, Wilhelm, Matthias, Michaud, Katarzyna, and Swiss Working Group on Sudden Cardiac Death
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Age Factors ,Autopsy ,Death, Sudden, Cardiac/etiology ,Family/psychology ,Forensic Pathology ,Genetic Counseling ,Genetic Predisposition to Disease ,Genetic Testing ,Humans ,Switzerland ,360 Social problems & social services ,education ,610 Medicine & health - Abstract
There is a need to standardise, within a coordinated Swiss framework, the practical aspects of genetic testing and genetic counselling on possibly inherited cardiovascular disorders in relatives of a sudden cardiac death (SCD) victim. Because of the major advances in genetic investigation techniques and recent publication of international guidelines in the field of cardiology, genetics and pathology, we consider it important to summarise the current evidence and propose an optimal approach to post-mortem genetic investigation for SCD victims and their families in Switzerland. In this article, we discuss important technical, financial and medico-ethical aspects, and provide updated information on specific situations in which forensic pathologists, general practitioners and cardiologists should suspect a genetic origin of the SCD. At present, the principles of benefit, the duty to warn and the impact of genetic information for family members at risk are considered as strong justifications for post-mortem disclosure and prevail over the arguments of respect for a deceased person's privacy and confidentiality. This paper underlines also the need to update and improve the general knowledge concerning the genetic risk of cardiovascular pathologies, the importance to perform an autopsy and post-mortem genetic testing in SCD victims, and to develop standardized post-mortem disclosure policy at national and international levels for SCD cases and relatives.
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- 2018
22. SCN5A mutations in 442 neonates and children: Genotype-phenotype correlation and identification of higher-risk subgroups
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Baruteau, Alban-Elouen, primary, Kyndt, Florence, additional, Behr, Elijah, additional, Vink, Arja, additional, Lachaud, Matthias, additional, Joong, Anna, additional, Schott, Jean-Jacques, additional, Horie, Minoru, additional, Denjoy, Isabelle, additional, Crotti, Lia, additional, Shimizu, Wataru, additional, Bos, Johan, additional, Stephenson, Elizabeth, additional, Wong, Leonie, additional, Abrams, Dominic, additional, Davis, Andrew, additional, Winbo, Annika, additional, Dubin, Anne, additional, Sanatani, Shubhayan, additional, Liberman, Leonardo, additional, Kaski, Juan-Pablo, additional, Rudic, Boris, additional, Kwok, Sit Yee, additional, Rieubland, Claudine, additional, Tfelt-Hansen, Jacob, additional, Van Hare, George, additional, Guyomarc’h-Delasalle, Béatrice, additional, Blom, Nico, additional, Wijeyeratne, Yanushi, additional, Gourraud, Jean-Baptiste, additional, Le Marec, Hervé, additional, Ozawa, Junichi, additional, Fressart, Véronique, additional, Lupoglazoff, Jean-Marc, additional, Dagradi, Federica, additional, Spazzolini, Carla, additional, Aiba, Takeshi, additional, Tester, David, additional, Zahavich, Laura, additional, Beauséjour-Ladouceur, Virginie, additional, Jadhav, Mangesh, additional, Skinner, Jonathan, additional, Franciosi, Sonia, additional, Krahn, Andrew, additional, Abdelsayed, Mena, additional, Ruben, Peter, additional, Yung, Tak-Cheung, additional, Ackerman, Michael, additional, Wilde, Arthur, additional, Schwartz, Peter, additional, and Probst, Vincent, additional
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- 2019
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23. Unexplained cardiac arrest:a tale of conflicting interpretations of KCNQ1 genetic test results
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Chua, Han Chow, Servatius, Helge, Asatryan, Babken, Schaller, André, Rieubland, Claudine, Noti, Fabian, Seiler, Jens, Roten, Laurent, Baldinger, Samuel H., Tanner, Hildegard, Fuhrer, Juerg, Haeberlin, Andreas, Lam, Anna, Pless, Stephan A., Medeiros-Domingo, Argelia, Chua, Han Chow, Servatius, Helge, Asatryan, Babken, Schaller, André, Rieubland, Claudine, Noti, Fabian, Seiler, Jens, Roten, Laurent, Baldinger, Samuel H., Tanner, Hildegard, Fuhrer, Juerg, Haeberlin, Andreas, Lam, Anna, Pless, Stephan A., and Medeiros-Domingo, Argelia
- Abstract
Objective: Unexplained cardiac arrest (UCA) is often the first manifestation of an inherited arrhythmogenic disease. Genetic testing in UCA is challenging due to the complexities of variant interpretation in the absence of supporting cardiac phenotype. We aimed to investigate if a KCNQ1 variant [p.(Pro64_Pro70del)], previously reported as pathogenic, contributes to the long-QT syndrome phenotype, co-segregates with disease or affects KCNQ1 function in vitro. Methods: DNA was extracted from peripheral blood of a 22-year-old male after resuscitation from UCA. Targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 190 clinically relevant cardiac genes with minor allele frequency < 1% were analyzed according to the guidelines of the American College of Medical Genetics. Functional characterization was performed using site-directed mutagenesis, expression in Xenopus laevis oocytes using the two-electrode voltage-clamp technique. Results: The 12-lead ECG, transthoracic echocardiography and coronary angiography after resuscitation showed no specific abnormalities. Two variants were identified: c.190_210del in-frame deletion in KCNQ1 (p.Pro64_Pro70del), reported previously as pathogenic and c.2431C > A in PKP2 (p.Arg811Ser), classified as likely benign. Two asymptomatic family members with no evident phenotype hosted the KCNQ1 variant. Functional studies showed that the wild-type and mutant channels have no significant differences in current levels, conductance-voltage relationships, as well as activation and deactivation kinetics, in the absence and presence of the auxiliary subunit KCNE1. Conclusions: Based on our data and previous reports, available evidence is insufficient to consider the variant KCNQ1:c.190_210del as pathogenic. Our findings call for cautious interpretation of genetic tests in UCA in the absence of a clinical phenotype.
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- 2018
24. SCN5A mutations in 442 neonates and children:genotype-phenotype correlation and identification of higher-risk subgroups
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Baruteau, Alban-Elouen, Kyndt, Florence, Behr, Elijah R, Vink, Arja S, Lachaud, Matthias, Joong, Anna, Schott, Jean-Jacques, Horie, Minoru, Denjoy, Isabelle, Crotti, Lia, Shimizu, Wataru, Bos, Johan M, Stephenson, Elizabeth A, Wong, Leonie, Abrams, Dominic J, Davis, Andrew M, Winbo, Annika, Dubin, Anne M, Sanatani, Shubhayan, Liberman, Leonardo, Kaski, Juan Pablo, Rudic, Boris, Kwok, Sit Yee, Rieubland, Claudine, Tfelt-Hansen, Jacob, Van Hare, George F, Guyomarc'h-Delasalle, Béatrice, Blom, Nico A, Wijeyeratne, Yanushi D, Gourraud, Jean-Baptiste, Le Marec, Hervé, Ozawa, Junichi, Fressart, Véronique, Lupoglazoff, Jean-Marc, Dagradi, Federica, Spazzolini, Carla, Aiba, Takeshi, Tester, David J, Zahavich, Laura A, Beauséjour-Ladouceur, Virginie, Jadhav, Mangesh, Skinner, Jonathan R, Franciosi, Sonia, Krahn, Andrew D, Abdelsayed, Mena, Ruben, Peter C, Yung, Tak-Cheung, Ackerman, Michael J, Wilde, Arthur A, Schwartz, Peter J, Probst, Vincent, Baruteau, Alban-Elouen, Kyndt, Florence, Behr, Elijah R, Vink, Arja S, Lachaud, Matthias, Joong, Anna, Schott, Jean-Jacques, Horie, Minoru, Denjoy, Isabelle, Crotti, Lia, Shimizu, Wataru, Bos, Johan M, Stephenson, Elizabeth A, Wong, Leonie, Abrams, Dominic J, Davis, Andrew M, Winbo, Annika, Dubin, Anne M, Sanatani, Shubhayan, Liberman, Leonardo, Kaski, Juan Pablo, Rudic, Boris, Kwok, Sit Yee, Rieubland, Claudine, Tfelt-Hansen, Jacob, Van Hare, George F, Guyomarc'h-Delasalle, Béatrice, Blom, Nico A, Wijeyeratne, Yanushi D, Gourraud, Jean-Baptiste, Le Marec, Hervé, Ozawa, Junichi, Fressart, Véronique, Lupoglazoff, Jean-Marc, Dagradi, Federica, Spazzolini, Carla, Aiba, Takeshi, Tester, David J, Zahavich, Laura A, Beauséjour-Ladouceur, Virginie, Jadhav, Mangesh, Skinner, Jonathan R, Franciosi, Sonia, Krahn, Andrew D, Abdelsayed, Mena, Ruben, Peter C, Yung, Tak-Cheung, Ackerman, Michael J, Wilde, Arthur A, Schwartz, Peter J, and Probst, Vincent
- Abstract
Aims: To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification.Methods and results: A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE.Conclusion: In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function.
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- 2018
25. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy
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Reinthaler, Eva M., Lal, Dennis, Lebon, Sebastien, Hildebrand, Michael S., Dahl, Hans-Henrik M., Regan, Brigid M., Feucht, Martha, Steinböck, Hannelore, Neophytou, Birgit, Ronen, Gabriel M., Roche, Laurian, Gruber-Sedlmayr, Ursula, Geldner, Julia, Haberlandt, Edda, Hoffmann, Per, Herms, Stefan, Gieger, Christian, Waldenberger, Melanie, Franke, Andre, Wittig, Michael, Schoch, Susanne, Becker, Albert J., Hahn, Andreas, Männik, Katrin, Toliat, Mohammad R., Winterer, Georg, Lerche, Holger, Nürnberg, Peter, Mefford, Heather, Scheffer, Ingrid E., Berkovic, Samuel F., Beckmann, Jacques S., Sander, Thomas, Jacquemont, Sebastien, Reymond, Alexandre, Zimprich, Fritz, Neubauer, Bernd A., Neubauer, Bernd, Mörzinger, Martina, Suls, Arvid, Weckhuysen, Sarah, Claes, Lieve, Deprez, Liesbet, Smets, Katrien, Van Dyck, Tine, Deconinck, Tine, De Jonghe, Peter, Møller, Rikke S., Klitten, Laura L., Hjalgrim, Helle, Campus, Kiel, Helbig, Ingo, Muhle, Hiltrud, Ostertag, Philipp, von Spiczak, Sarah, Stephani, Ulrich, Trucks, Holger, Elger, Christian E., Kleefuß-Lie, Ailing A., Kunz, Wolfram S., Surges, Rainer, Gaus, Verena, Janz, Dieter, Schmitz, Bettina, Rosenow, Felix, Klein, Karl Martin, Reif, Philipp S., Oertel, Wolfgang H., Hamer, Hajo M., Becker, Felicitas, Weber, Yvonne, Koeleman, Bobby P.C., de Kovel, Carolien, Lindhout, Dick, Ameil, Agnès, Andrieux, Joris, Bouquillon, Sonia, Boute, Odile, de Flandre, Jeanne, Cuisset, Jean Marie, Cuvellier, Jean-Christophe, Salengro, Roger, David, Albert, de Vries, Bert, Delrue, Marie-Ange, Doco-Fenzy, Martine, Fernandez, Bridget A., Heron, Delphine, Keren, Boris, Lebel, Robert, Leheup, Bruno, Lewis, Suzanne, Mencarelli, Maria Antonietta, Mignot, Cyril, Minet, Jean-Claude, Moerman, Alexandre, Morice-Picard, Fanny, Mucciolo, Mafalda, Ounap, Katrin, Pasquier, Laurent, Petit, Florence, Ragona, Francesca, Rajcan-Separovic, Evica, Renieri, Alessandra, Rieubland, Claudine, Sanlaville, Damien, Sarrazin, Elisabeth, Shen, Yiping, van Haelst, Mieke, and Silfhout, Anneke Vulto-van
- Abstract
Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE
- Published
- 2017
26. Clinical delineation, sex differences, and genotype–phenotype correlation in pathogenic KDM6Avariants causing X-linked Kabuki syndrome type 2
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Faundes, Víctor, Goh, Stephanie, Akilapa, Rhoda, Bezuidenhout, Heidre, Bjornsson, Hans T., Bradley, Lisa, Brady, Angela F., Brischoux-Boucher, Elise, Brunner, Han, Bulk, Saskia, Canham, Natalie, Cody, Declan, Dentici, Maria Lisa, Digilio, Maria Cristina, Elmslie, Frances, Fry, Andrew E., Gill, Harinder, Hurst, Jane, Johnson, Diana, Julia, Sophie, Lachlan, Katherine, Lebel, Robert Roger, Byler, Melissa, Gershon, Eric, Lemire, Edmond, Gnazzo, Maria, Lepri, Francesca Romana, Marchese, Antonia, McEntagart, Meriel, McGaughran, Julie, Mizuno, Seiji, Okamoto, Nobuhiko, Rieubland, Claudine, Rodgers, Jonathan, Sasaki, Erina, Scalais, Emmanuel, Scurr, Ingrid, Suri, Mohnish, van der Burgt, Ineke, Matsumoto, Naomichi, Miyake, Noriko, Benoit, Valérie, Lederer, Damien, and Banka, Siddharth
- Abstract
The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood.
- Published
- 2021
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27. SCN5A mutations in 442 neonates and children: genotype–phenotype correlation and identification of higher-risk subgroups
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Baruteau, Alban-Elouen, primary, Kyndt, Florence, additional, Behr, Elijah R, additional, Vink, Arja S, additional, Lachaud, Matthias, additional, Joong, Anna, additional, Schott, Jean-Jacques, additional, Horie, Minoru, additional, Denjoy, Isabelle, additional, Crotti, Lia, additional, Shimizu, Wataru, additional, Bos, Johan M, additional, Stephenson, Elizabeth A, additional, Wong, Leonie, additional, Abrams, Dominic J, additional, Davis, Andrew M, additional, Winbo, Annika, additional, Dubin, Anne M, additional, Sanatani, Shubhayan, additional, Liberman, Leonardo, additional, Kaski, Juan Pablo, additional, Rudic, Boris, additional, Kwok, Sit Yee, additional, Rieubland, Claudine, additional, Tfelt-Hansen, Jacob, additional, Van Hare, George F, additional, Guyomarc’h-Delasalle, Béatrice, additional, Blom, Nico A, additional, Wijeyeratne, Yanushi D, additional, Gourraud, Jean-Baptiste, additional, Le Marec, Hervé, additional, Ozawa, Junichi, additional, Fressart, Véronique, additional, Lupoglazoff, Jean-Marc, additional, Dagradi, Federica, additional, Spazzolini, Carla, additional, Aiba, Takeshi, additional, Tester, David J, additional, Zahavich, Laura A, additional, Beauséjour-Ladouceur, Virginie, additional, Jadhav, Mangesh, additional, Skinner, Jonathan R, additional, Franciosi, Sonia, additional, Krahn, Andrew D, additional, Abdelsayed, Mena, additional, Ruben, Peter C, additional, Yung, Tak-Cheung, additional, Ackerman, Michael J, additional, Wilde, Arthur A, additional, Schwartz, Peter J, additional, and Probst, Vincent, additional
- Published
- 2018
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28. Phenotypes and genotypes in individuals with SMC1A variants
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Huisman, Sylvia, Mulder, Paul A, Redeker, Egbert, Bader, Ingrid, Bisgaard, Anne-Marie, Brooks, Alice, Cereda, Anna, Cinca, Constanza, Clark, Dinah, Cormier-Daire, Valerie, Deardorff, Matthew A, Diderich, Karin, Elting, Mariet, van Essen, Anthonie, FitzPatrick, David, Gervasini, Cristina, Gillessen-Kaesbach, Gabriele, Girisha, Katta M, Hilhorst-Hofstee, Yvonne, Hopman, Saskia, Horn, Denise, Isrie, Mala, Jansen, Sandra, Jespersgaard, Cathrine, Kaiser, Frank J, Kaur, Maninder, Kleefstra, Tjitske, Krantz, Ian D, Lakeman, Phillis, Landlust, Annemiek, Lessel, Davor, Michot, Caroline, Moss, Jo, Noon, Sarah E, Oliver, Chris, Parenti, Ilaria, Pie, Juan, Ramos, Feliciano J, Rieubland, Claudine, Russo, Silvia, Selicorni, Angelo, Tümer, Zeynep, Vorstenbosch, Rieneke, Wenger, Tara L, van Balkom, Ingrid, Piening, Sigrid, Wierzba, Jolanta, Hennekam, Raoul C, Huisman, Sylvia, Mulder, Paul A, Redeker, Egbert, Bader, Ingrid, Bisgaard, Anne-Marie, Brooks, Alice, Cereda, Anna, Cinca, Constanza, Clark, Dinah, Cormier-Daire, Valerie, Deardorff, Matthew A, Diderich, Karin, Elting, Mariet, van Essen, Anthonie, FitzPatrick, David, Gervasini, Cristina, Gillessen-Kaesbach, Gabriele, Girisha, Katta M, Hilhorst-Hofstee, Yvonne, Hopman, Saskia, Horn, Denise, Isrie, Mala, Jansen, Sandra, Jespersgaard, Cathrine, Kaiser, Frank J, Kaur, Maninder, Kleefstra, Tjitske, Krantz, Ian D, Lakeman, Phillis, Landlust, Annemiek, Lessel, Davor, Michot, Caroline, Moss, Jo, Noon, Sarah E, Oliver, Chris, Parenti, Ilaria, Pie, Juan, Ramos, Feliciano J, Rieubland, Claudine, Russo, Silvia, Selicorni, Angelo, Tümer, Zeynep, Vorstenbosch, Rieneke, Wenger, Tara L, van Balkom, Ingrid, Piening, Sigrid, Wierzba, Jolanta, and Hennekam, Raoul C
- Abstract
SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.
- Published
- 2017
29. Chronic pancreatitis in childhood – would you think about genetics?
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Fluri, S., Stranzinger, Enno, Trachsel, T., Wiest, Reiner, Ambuehl, J., Schibli, Susanne, and Rieubland, Claudine
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610 Medicine & health - Published
- 2016
30. 15q26.1 microdeletion encompassing only CHD2 and RGMA in two adults with moderate intellectual disability, epilepsy and truncal obesity
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Courage, Carolina, Houge, Gunnar, Gallati, Sabina, Schjelderup, Jack, and Rieubland, Claudine
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- 2014
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31. 96-77: Phenotypic Spectrum of HCN4 Mutations: Further Evidence of involvement in Left Ventricular Non-Compaction, Sick Sinus Syndrome, and Mood- and Anxiety Disorder
- Author
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Servatius, Helge, primary, Pless, Stephan A., additional, Schaller, Andre, additional, Lynagh, Timothy, additional, Tanner, Hildegard, additional, Rieubland, Claudine, additional, Roten, Laurent, additional, Seiler, Jens, additional, Noti, Fabian, additional, Tran, V. Nam, additional, Haeberlin, Andreas, additional, Lam, Anna, additional, Gallati, Sabina, additional, Fuhrer, Juerg, additional, and Domingo, Argelia Medeiros, additional
- Published
- 2016
- Full Text
- View/download PDF
32. Sudden cardiac death in forensic medicine – Swiss recommendations for a multidisciplinary approach
- Author
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Wilhelm, M, Bolliger, Stephan A, Bartsch, Christine, Fokstuen, S, Gräni, Christoph, Martos, Viktor, Medeiros Domingo, Argelia, Osculati, Antonio, Rieubland, Claudine, Sabatasso, Sara, Saguner, Ardan M, Schyma, Christian, Tschui, Joelle, Wyler, Daniel, Bhuiyan, Zahurul A, Fellmann, Florence, Michaud, Katarzyna, Wilhelm, M, Bolliger, Stephan A, Bartsch, Christine, Fokstuen, S, Gräni, Christoph, Martos, Viktor, Medeiros Domingo, Argelia, Osculati, Antonio, Rieubland, Claudine, Sabatasso, Sara, Saguner, Ardan M, Schyma, Christian, Tschui, Joelle, Wyler, Daniel, Bhuiyan, Zahurul A, Fellmann, Florence, and Michaud, Katarzyna
- Abstract
Sudden cardiac death (SCD) is by definition unexpected and cardiac in nature. The investigation is almost invariably performed by a forensic pathologist. Under these circumstances the role of the forensic pathologist is twofold: (1.) to determine rapidly and efficiently the cause and manner of death and (2.) to initiate a multidisciplinary process in order to prevent further deaths in existing family members. If the death is determined to be due to “natural” causes the district attorney in charge often refuses further examinations. However, additional examinations, i.e. extensive histopathological investigations and/or molecular genetic analyses, are necessary in many cases to clarify the cause of death. The Swiss Society of Legal Medicine created a multidisciplinary working group together with clinical and molecular geneticists and cardiologists in the hope of harmonising the approach to investigate SCD. The aim of this paper is to close the gap between the Swiss recommendations for routine forensic post-mortem cardiac examination and clinical recommendations for genetic testing of inherited cardiac diseases; this is in order to optimise the diagnostic procedures and preventive measures for living family members. The key points of the recommendations are (1.) the forensic autopsy procedure for all SCD victims under 40 years of age, (2.) the collection and storage of adequate samples for genetic testing, (3.) communication with the families, and (4.) a multidisciplinary approach including cardiogenetic counselling.
- Published
- 2015
33. Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia
- Author
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Desmaison, Annaïck, Vigouroux, Adeline, Rieubland, Claudine, Peres, Christine, Calvas, Patrick, and Chassaing, Nicolas
- Subjects
Homeodomain Proteins ,congenital, hereditary, and neonatal diseases and abnormalities ,Base Sequence ,LIM-Homeodomain Proteins ,Molecular Sequence Data ,Mutation, Missense ,Anophthalmos ,eye diseases ,Cohort Studies ,Amino Acid Sequence ,Anophthalmos/genetics ,Conserved Sequence/genetics ,Homeodomain Proteins/chemistry ,Homeodomain Proteins/genetics ,Humans ,Microphthalmos/genetics ,Mutation, Missense/genetics ,Transcription Factors/chemistry ,Transcription Factors/genetics ,embryonic structures ,Microphthalmos ,Conserved Sequence ,Research Article ,Transcription Factors - Abstract
Purpose: Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (orthodenticle homeobox 2 [OTX2], retina and anterior neural fold homeobox [RAX], SRY-box 2 [SOX2], CEH10 homeodomain-containing homolog [CHX10], and growth differentiation factor 6 [GDF6]) have been implicated mainly in isolated micro/anophthalmia but causative mutations of these genes explain less than a quarter of these developmental defects. The essential role of the LIM homeobox 2 (LHX2) transcription factor in early eye development has recently been documented. We postulated that mutations in this gene could lead to micro/anophthalmia, and thus performed molecular screening of its sequence in patients having micro/anophthalmia. Methods: Seventy patients having non-syndromic forms of colobomatous microphthalmia (n=25), isolated microphthalmia (n=18), or anophthalmia (n=17), and syndromic forms of micro/anophthalmia (n=10) were included in this study after negative molecular screening for OTX2, RAX, SOX2, and CHX10 mutations. Mutation screening of LHX2 was performed by direct sequencing of the coding sequences and intron/exon boundaries. Results: Two heterozygous variants of unknown significance (c.128C > G [p.Pro43Arg]; c.776C > A [p.Pro259Gln]) were identified in LHX2 among the 70 patients. These variations were not identified in a panel of 100 control patients of mixed origins. The variation c.776C > A (p.Pro259Gln) was considered as non pathogenic by in silico analysis, while the variation c.128C > G (p.Pro43Arg) considered as deleterious by in silico analysis and was inherited from the asymptomatic father. Conclusions: Mutations in LHX2 do not represent a frequent cause of micro/anophthalmia.
- Published
- 2010
34. Phenotypic and molecular characterization of a novel case of dyssegmental dysplasia, Silverman-Handmaker type
- Author
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Rieubland, Claudine, Jacquemont, Sebastien, Mittaz, Laureane, Osterheld, Maria-Chiara, Vial, Yvan, Superti-Furga, Andrea, Unger, Sheila, and Bonafé, Luisa
- Published
- 2010
- Full Text
- View/download PDF
35. Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome: five cases with intragenic mutations or complete deletions of GLI3
- Author
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Hurst, Jane A, Jenkins, Dagan, Vasudevan, Pradeep C, Kirchhoff, Eva Maria, Skovby, Flemming, Rieubland, Claudine, Gallati, Sabina, Rittinger, Olaf, Kroisel, Peter M, Johnson, David, Biesecker, Leslie G, Wilkie, Andrew O M, Hurst, Jane A, Jenkins, Dagan, Vasudevan, Pradeep C, Kirchhoff, Eva Maria, Skovby, Flemming, Rieubland, Claudine, Gallati, Sabina, Rittinger, Olaf, Kroisel, Peter M, Johnson, David, Biesecker, Leslie G, and Wilkie, Andrew O M
- Abstract
Greig cephalopolysyndactyly syndrome (GCPS) is a multiple congenital malformation characterised by limb and craniofacial anomalies, caused by heterozygous mutation or deletion of GLI3. We report four boys and a girl who were presented with trigonocephaly due to metopic synostosis, in association with pre- and post-axial polydactyly and cutaneous syndactyly of hands and feet. Two cases had additional sagittal synostosis. None had a family history of similar features. In all five children, the diagnosis of GCPS was confirmed by molecular analysis of GLI3 (two had intragenic mutations and three had complete gene deletions detected on array comparative genomic hybridisation), thus highlighting the importance of trigonocephaly or overt metopic or sagittal synostosis as a distinct presenting feature of GCPS. These observations confirm and extend a recently proposed association of intragenic GLI3 mutations with metopic synostosis; moreover, the three individuals with complete deletion of GLI3 were previously considered to have Carpenter syndrome, highlighting an important source of diagnostic confusion.
- Published
- 2011
36. Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome: five cases with intragenic mutations or complete deletions of GLI3
- Author
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Hurst, Jane A, primary, Jenkins, Dagan, additional, Vasudevan, Pradeep C, additional, Kirchhoff, Maria, additional, Skovby, Flemming, additional, Rieubland, Claudine, additional, Gallati, Sabina, additional, Rittinger, Olaf, additional, Kroisel, Peter M, additional, Johnson, David, additional, Biesecker, Leslie G, additional, and Wilkie, Andrew OM, additional
- Published
- 2011
- Full Text
- View/download PDF
37. Uncombable hair syndrome: A clinical report
- Author
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Rieubland, Claudine, de Viragh, Pierre A., and Addor, Marie-Claude
- Published
- 2007
- Full Text
- View/download PDF
38. Functional Consequences of aSDHBGene Mutation in an Apparently Sporadic Pheochromocytoma
- Author
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Gimenez-Roqueplo, Anne-Paule, primary, Favier, Judith, additional, Rustin, Pierre, additional, Rieubland, Claudine, additional, Kerlan, Véronique, additional, Plouin, Pierre-François, additional, Rötig, Agnès, additional, and Jeunemaitre, Xavier, additional
- Published
- 2002
- Full Text
- View/download PDF
39. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy
- Author
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Reinthaler, Eva M., Lal, Dennis, Lebon, Sebastien, Hildebrand, Michael S., Dahl, Hans-Henrik M., Regan, Brigid M., Feucht, Martha, Steinböck, Hannelore, Neophytou, Birgit, Ronen, Gabriel M., Roche, Laurian, Gruber-Sedlmayr, Ursula, Geldner, Julia, Haberlandt, Edda, Hoffmann, Per, Herms, Stefan, Gieger, Christian, Waldenberger, Melanie, Franke, Andre, Wittig, Michael, Schoch, Susanne, Becker, Albert J., Hahn, Andreas, Männik, Katrin, Toliat, Mohammad R., Winterer, Georg, Lerche, Holger, Nürnberg, Peter, Mefford, Heather, Scheffer, Ingrid E., Berkovic, Samuel F., Beckmann, Jacques S., Sander, Thomas, Jacquemont, Sebastien, Reymond, Alexandre, Zimprich, Fritz, Neubauer, Bernd A., Neubauer, Bernd, Mörzinger, Martina, Suls, Arvid, Weckhuysen, Sarah, Claes, Lieve, Deprez, Liesbet, Smets, Katrien, Van Dyck, Tine, Deconinck, Tine, De Jonghe, Peter, Møller, Rikke S., Klitten, Laura L., Hjalgrim, Helle, Campus, Kiel, Helbig, Ingo, Muhle, Hiltrud, Ostertag, Philipp, von Spiczak, Sarah, Stephani, Ulrich, Trucks, Holger, Elger, Christian E., Kleefuß-Lie, Ailing A., Kunz, Wolfram S., Surges, Rainer, Gaus, Verena, Janz, Dieter, Schmitz, Bettina, Rosenow, Felix, Klein, Karl Martin, Reif, Philipp S., Oertel, Wolfgang H., Hamer, Hajo M., Becker, Felicitas, Weber, Yvonne, Koeleman, Bobby P.C., de Kovel, Carolien, Lindhout, Dick, Ameil, Agnès, Andrieux, Joris, Bouquillon, Sonia, Boute, Odile, de Flandre, Jeanne, Cuisset, Jean Marie, Cuvellier, Jean-Christophe, Salengro, Roger, David, Albert, de Vries, Bert, Delrue, Marie-Ange, Doco-Fenzy, Martine, Fernandez, Bridget A., Heron, Delphine, Keren, Boris, Lebel, Robert, Leheup, Bruno, Lewis, Suzanne, Mencarelli, Maria Antonietta, Mignot, Cyril, Minet, Jean-Claude, Moerman, Alexandre, Morice-Picard, Fanny, Mucciolo, Mafalda, Ounap, Katrin, Pasquier, Laurent, Petit, Florence, Ragona, Francesca, Rajcan-Separovic, Evica, Renieri, Alessandra, Rieubland, Claudine, Sanlaville, Damien, Sarrazin, Elisabeth, Shen, Yiping, van Haelst, Mieke, Silfhout, Anneke Vulto-van, Reinthaler, Eva M., Lal, Dennis, Lebon, Sebastien, Hildebrand, Michael S., Dahl, Hans-Henrik M., Regan, Brigid M., Feucht, Martha, Steinböck, Hannelore, Neophytou, Birgit, Ronen, Gabriel M., Roche, Laurian, Gruber-Sedlmayr, Ursula, Geldner, Julia, Haberlandt, Edda, Hoffmann, Per, Herms, Stefan, Gieger, Christian, Waldenberger, Melanie, Franke, Andre, Wittig, Michael, Schoch, Susanne, Becker, Albert J., Hahn, Andreas, Männik, Katrin, Toliat, Mohammad R., Winterer, Georg, Lerche, Holger, Nürnberg, Peter, Mefford, Heather, Scheffer, Ingrid E., Berkovic, Samuel F., Beckmann, Jacques S., Sander, Thomas, Jacquemont, Sebastien, Reymond, Alexandre, Zimprich, Fritz, Neubauer, Bernd A., Neubauer, Bernd, Mörzinger, Martina, Suls, Arvid, Weckhuysen, Sarah, Claes, Lieve, Deprez, Liesbet, Smets, Katrien, Van Dyck, Tine, Deconinck, Tine, De Jonghe, Peter, Møller, Rikke S., Klitten, Laura L., Hjalgrim, Helle, Campus, Kiel, Helbig, Ingo, Muhle, Hiltrud, Ostertag, Philipp, von Spiczak, Sarah, Stephani, Ulrich, Trucks, Holger, Elger, Christian E., Kleefuß-Lie, Ailing A., Kunz, Wolfram S., Surges, Rainer, Gaus, Verena, Janz, Dieter, Schmitz, Bettina, Rosenow, Felix, Klein, Karl Martin, Reif, Philipp S., Oertel, Wolfgang H., Hamer, Hajo M., Becker, Felicitas, Weber, Yvonne, Koeleman, Bobby P.C., de Kovel, Carolien, Lindhout, Dick, Ameil, Agnès, Andrieux, Joris, Bouquillon, Sonia, Boute, Odile, de Flandre, Jeanne, Cuisset, Jean Marie, Cuvellier, Jean-Christophe, Salengro, Roger, David, Albert, de Vries, Bert, Delrue, Marie-Ange, Doco-Fenzy, Martine, Fernandez, Bridget A., Heron, Delphine, Keren, Boris, Lebel, Robert, Leheup, Bruno, Lewis, Suzanne, Mencarelli, Maria Antonietta, Mignot, Cyril, Minet, Jean-Claude, Moerman, Alexandre, Morice-Picard, Fanny, Mucciolo, Mafalda, Ounap, Katrin, Pasquier, Laurent, Petit, Florence, Ragona, Francesca, Rajcan-Separovic, Evica, Renieri, Alessandra, Rieubland, Claudine, Sanlaville, Damien, Sarrazin, Elisabeth, Shen, Yiping, van Haelst, Mieke, and Silfhout, Anneke Vulto-van
- Abstract
Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE
40. Recommendations for genetic testing and counselling after sudden cardiac death: practical aspects for Swiss practice.
- Author
-
Medeiros Domingo A, Bolliger S, Gräni C, Rieubland C, Hersch D, Asatryan B, Schyma C, Saguner A, Wyler D, Bhuiyan Z, Fellman F, Osculati AM, Ringger R, Fokstuen S, Sabatasso S, Wilhelm M, and Michaud K
- Subjects
- Age Factors, Autopsy, Forensic Pathology, Humans, Switzerland, Death, Sudden, Cardiac etiology, Family psychology, Genetic Counseling, Genetic Predisposition to Disease, Genetic Testing
- Abstract
There is a need to standardise, within a coordinated Swiss framework, the practical aspects of genetic testing and genetic counselling on possibly inherited cardiovascular disorders in relatives of a sudden cardiac death (SCD) victim. Because of the major advances in genetic investigation techniques and recent publication of international guidelines in the field of cardiology, genetics and pathology, we consider it important to summarise the current evidence and propose an optimal approach to post-mortem genetic investigation for SCD victims and their families in Switzerland. In this article, we discuss important technical, financial and medico-ethical aspects, and provide updated information on specific situations in which forensic pathologists, general practitioners and cardiologists should suspect a genetic origin of the SCD. At present, the principles of benefit, the duty to warn and the impact of genetic information for family members at risk are considered as strong justifications for post-mortem disclosure and prevail over the arguments of respect for a deceased person's privacy and confidentiality. This paper underlines also the need to update and improve the general knowledge concerning the genetic risk of cardiovascular pathologies, the importance to perform an autopsy and post-mortem genetic testing in SCD victims, and to develop standardized post-mortem disclosure policy at national and international levels for SCD cases and relatives.
- Published
- 2018
- Full Text
- View/download PDF
41. Sudden cardiac death in forensic medicine – Swiss recommendations for a multidisciplinary approach.
- Author
-
Wilhelm M, Bolliger SA, Bartsch C, Fokstuen S, Gräni C, Martos V, Medeiros Domingo A, Osculati A, Rieubland C, Sabatasso S, Saguner AM, Schyma C, Tschui J, Wyler D, Bhuiyan ZA, Fellmann F, and Michaud K
- Subjects
- Age Factors, Cause of Death, Communication, Genetic Predisposition to Disease, Humans, Switzerland, Autopsy methods, Death, Sudden, Cardiac etiology, Family, Forensic Pathology methods, Genetic Testing methods
- Abstract
Sudden cardiac death (SCD) is by definition unexpected and cardiac in nature. The investigation is almost invariably performed by a forensic pathologist. Under these circumstances the role of the forensic pathologist is twofold: (1.) to determine rapidly and efficiently the cause and manner of death and (2.) to initiate a multidisciplinary process in order to prevent further deaths in existing family members. If the death is determined to be due to "natural" causes the district attorney in charge often refuses further examinations. However, additional examinations, i.e. extensive histopathological investigations and/or molecular genetic analyses, are necessary in many cases to clarify the cause of death. The Swiss Society of Legal Medicine created a multidisciplinary working group together with clinical and molecular geneticists and cardiologists in the hope of harmonising the approach to investigate SCD. The aim of this paper is to close the gap between the Swiss recommendations for routine forensic post-mortem cardiac examination and clinical recommendations for genetic testing of inherited cardiac diseases; this is in order to optimise the diagnostic procedures and preventive measures for living family members. The key points of the recommendations are (1.) the forensic autopsy procedure for all SCD victims under 40 years of age, (2.) the collection and storage of adequate samples for genetic testing, (3.) communication with the families, and (4.) a multidisciplinary approach including cardiogenetic counselling.
- Published
- 2015
- Full Text
- View/download PDF
42. Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia.
- Author
-
Desmaison A, Vigouroux A, Rieubland C, Peres C, Calvas P, and Chassaing N
- Subjects
- Amino Acid Sequence, Base Sequence, Cohort Studies, Conserved Sequence genetics, Homeodomain Proteins chemistry, Humans, LIM-Homeodomain Proteins, Molecular Sequence Data, Transcription Factors chemistry, Anophthalmos genetics, Homeodomain Proteins genetics, Microphthalmos genetics, Mutation, Missense genetics, Transcription Factors genetics
- Abstract
Purpose: Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (orthodenticle homeobox 2 [OTX2], retina and anterior neural fold homeobox [RAX], SRY-box 2 [SOX2], CEH10 homeodomain-containing homolog [CHX10], and growth differentiation factor 6 [GDF6]) have been implicated mainly in isolated micro/anophthalmia but causative mutations of these genes explain less than a quarter of these developmental defects. The essential role of the LIM homeobox 2 (LHX2) transcription factor in early eye development has recently been documented. We postulated that mutations in this gene could lead to micro/anophthalmia, and thus performed molecular screening of its sequence in patients having micro/anophthalmia., Methods: Seventy patients having non-syndromic forms of colobomatous microphthalmia (n=25), isolated microphthalmia (n=18), or anophthalmia (n=17), and syndromic forms of micro/anophthalmia (n=10) were included in this study after negative molecular screening for OTX2, RAX, SOX2, and CHX10 mutations. Mutation screening of LHX2 was performed by direct sequencing of the coding sequences and intron/exon boundaries., Results: Two heterozygous variants of unknown significance (c.128C>G [p.Pro43Arg]; c.776C>A [p.Pro259Gln]) were identified in LHX2 among the 70 patients. These variations were not identified in a panel of 100 control patients of mixed origins. The variation c.776C>A (p.Pro259Gln) was considered as non pathogenic by in silico analysis, while the variation c.128C>G (p.Pro43Arg) considered as deleterious by in silico analysis and was inherited from the asymptomatic father., Conclusions: Mutations in LHX2 do not represent a frequent cause of micro/anophthalmia.
- Published
- 2010
43. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas.
- Author
-
Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, Khau Van Kien P, Corvol P, Plouin PF, and Jeunemaitre X
- Subjects
- Adrenal Gland Neoplasms blood supply, Adrenal Gland Neoplasms enzymology, Adult, DNA, Neoplasm genetics, Female, Germ-Line Mutation, Humans, Iron-Sulfur Proteins, Loss of Heterozygosity, Male, Middle Aged, Pheochromocytoma blood supply, Pheochromocytoma enzymology, Urinary Bladder Neoplasms blood supply, Urinary Bladder Neoplasms enzymology, Urinary Bladder Neoplasms genetics, Adrenal Gland Neoplasms genetics, Pheochromocytoma genetics, Protein Subunits genetics, Succinate Dehydrogenase genetics
- Abstract
Germ-line mutations in the genes encoding succinate dehydrogenase complex subunits B (SDHB) and D (SDHD) have been reported in familial paragangliomas and apparently sporadic phaeochromocytomas (ASP), but the genotype-phenotype relationships of these mutations are unknown. Eighty-four patients (all but 2 followed up for 8.8 +/- 5.7 years) with ASP (57 with adrenal tumors, 27 with extra-adrenal, multiple, malignant, or recurrent tumors) were screened for the major susceptibility genes for phaeochromocytoma (RET, VHL, SDHD, and SDHB). Thirty-three tumors were available for molecular analysis, enzyme assays, and immunohistochemistry. No (0%) RET and 2 (2.4%) VHL mutations were detected. Only two coding single nucleotide polymorphisms in the SDHD gene (G12S and H50R) were found in 6 patients (7%). Conversely, six deleterious mutations in the SDHB gene were identified in 8 patients (9.5%). Ectopic site and recurrence or malignancy were strongly associated with SDHB mutations (7 of 8, 87%, versus 20 of 76, 26%; P = 0.001). Somatic DNA analysis indicated a loss of heterozygosity at chromosome 1p36 (SDHB locus) in 16 of 33 cases (48%). A loss of heterozygosity at the SDHB locus was found in all tumors with SDHB mutation, and assays of respiratory chain enzymes showed a complete loss of complex II catalytic activity. The vascular architecture of tumors with SDHB mutations displayed features typical of malignancy. These data strongly suggest that SDHB gene is a tumor suppressor gene and that the identification of germ-line mutations in SDHB gene in patients with ASPs should be considered as a high-risk factor for malignancy or recurrence.
- Published
- 2003
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