39 results on '"Rieubland, Claudine"'
Search Results
2. Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders
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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
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- 2023
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3. Correction: Clinical and genetic analysis further delineates the phenotypic spectrum of ALDH1A3-related anophthalmia and microphthalmia
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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
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- 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
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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
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- 2021
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5. De novo variants predicting haploinsufficiency for DIP2C are associated with expressive speech delay.
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Ha, Thoa, Morgan, Angela, Bartos, Meghan N., Beatty, Katelyn, Cogné, Benjamin, Braun, Dominique, Gerber, Céline B., Gaspar, Harald, Kopps, Anna M., Rieubland, Claudine, Hurst, Anna C. E., Amor, David J., Nizon, Mathilde, Pasquier, Laurent, Pfundt, Rolph, Reis, André, Siu, Victoria Mok, Tessarech, Marine, Thompson, Michelle L., and Vincent, Marie
- Abstract
The disconnected (disco)‐interacting protein 2 (DIP2) gene was first identified in D. melanogaster and contains a DNA methyltransferase‐associated protein 1 (DMAP1) binding domain, Acyl‐CoA synthetase domain and AMP‐binding sites. DIP2 regulates axonal bifurcation of the mushroom body neurons in D. melanogaster and is required for axonal regeneration in the neurons of C. elegans. The DIP2 homologues in vertebrates, Disco‐interacting protein 2 homolog A (DIP2A), Disco‐interacting protein 2 homolog B (DIP2B), and Disco‐interacting protein 2 homolog C (DIP2C), are highly conserved and expressed widely in the central nervous system. Although there is evidence that DIP2C plays a role in cognition, reports of pathogenic variants in these genes are rare and their significance is uncertain. We present 23 individuals with heterozygous DIP2C variants, all manifesting developmental delays that primarily affect expressive language and speech articulation. Eight patients had de novo variants predicting loss‐of‐function in the DIP2C gene, two patients had de novo missense variants, three had paternally inherited loss of function variants and six had maternally inherited loss‐of‐function variants, while inheritance was unknown for four variants. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects, and bicuspid aortic valve). Minor facial anomalies were inconsistent but included a high anterior hairline with a long forehead, broad nasal tip, and ear anomalies. Brainspan analysis showed elevated DIP2C expression in the human neocortex at 10–24 weeks after conception. With the cases presented herein, we provide phenotypic and genotypic data supporting the association between loss‐of‐function variants in DIP2C with a neurocognitive phenotype. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Enhancing fetal outcomes in GCK-MODY pregnancies: a precision medicine approach via non-invasive prenatal GCK mutation detection.
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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
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- 2024
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7. Functional characterization of a novel SCN5A variant associated with long QT syndrome and sudden cardiac death
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Neubauer, Jacqueline, Wang, Zizun, Rougier, Jean-Sébastien, Abriel, Hugues, Rieubland, Claudine, Bartholdi, Deborah, Haas, Cordula, and Medeiros-Domingo, Argelia
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- 2019
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8. Expanding Genotype/Phenotype Correlation in 2p11.2-p12 Microdeletion Syndrome.
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Ferrario, Alessandra, Aliu, Nijas, Rieubland, Claudine, Vuilleumier, Sébastian, Grabe, Hilary M., and Escher, Pascal
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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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9. 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., and Medeiros-Domingo, Argelia
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- 2018
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10. Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome
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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.
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- 2015
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11. Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology.
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Banka, Siddharth, Bennington, Abigail, Baker, Martin J, Rijckmans, Ellen, Clemente, Giuliana D, Ansor, Nurhuda Mohamad, Sito, Hilary, Prasad, Pritha, Anyane-Yeboa, Kwame, Badalato, Lauren, Dimitrov, Boyan, Fitzpatrick, David, Hurst, Anna C E, Jansen, Anna C, Kelly, Melissa A, Krantz, Ian, Rieubland, Claudine, Ross, Meredith, Rudy, Natasha L, and Sanz, Javier
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RHO GTPases ,MORPHOLOGY ,MISSENSE mutation ,DEVELOPMENTAL delay ,SYNDROMES ,INTELLECTUAL disabilities - Abstract
RAC1 is a highly conserved Rho GTPase critical for many cellular and developmental processes. De novo missense RAC1 variants cause a highly variable neurodevelopmental disorder. Some of these variants have previously been shown to have a dominant negative effect. Most previously reported patients with this disorder have either severe microcephaly or severe macrocephaly. Here, we describe eight patients with pathogenic missense RAC1 variants affecting residues between Q61 and R68 within the switch II region of RAC1. These patients display variable combinations of developmental delay, intellectual disability, brain anomalies such as polymicrogyria and cardiovascular defects with normocephaly or relatively milder micro- or macrocephaly. Pulldown assays, NIH3T3 fibroblast spreading assays and staining for activated PAK1/2/3 and WAVE2 suggest that these variants increase RAC1 activity and over-activate downstream signalling targets. Axons of neurons isolated from Drosophila embryos expressing the most common of the activating variants are significantly shorter, with an increased density of filopodial protrusions. In vivo , these embryos exhibit frequent defects in axonal organization. Class IV dendritic arborization neurons expressing this variant exhibit a significant reduction in the total area of the dendritic arbour, increased branching and failure of self-avoidance. RNAi knock down of the WAVE regulatory complex component Cyfip significantly rescues these morphological defects. These results establish that activating substitutions affecting residues Q61–R68 within the switch II region of RAC1 cause a developmental syndrome. Our findings reveal that these variants cause altered downstream signalling, resulting in abnormal neuronal morphology and reveal the WAVE regulatory complex/Arp2/3 pathway as a possible therapeutic target for activating RAC1 variants. These insights also have the potential to inform the mechanism and therapy for other disorders caused by variants in genes encoding other Rho GTPases, their regulators and downstream effectors. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Compound‐heterozygous GRIN2A null variants associated with severe developmental and epileptic encephalopathy.
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Strehlow, Vincent, Rieubland, Claudine, Gallati, Sabina, Kim, Sukhan, Myers, Scott J., Peterson, Vincent, Ramsey, Amy J., Teuscher, Daniel D., Traynelis, Stephen F., and Lemke, Johannes R.
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BRAIN diseases , *LENNOX-Gastaut syndrome , *GENETIC variation , *PEOPLE with epilepsy , *METHYL aspartate receptors , *INDIVIDUALIZED medicine , *KETAMINE - 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. [ABSTRACT FROM AUTHOR]
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- 2022
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13. 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., 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
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- 2014
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14. Duplication of the sodium channel gene cluster on 2q24 in children with early onset epilepsy
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Goeggel Simonetti, Barbara, Rieubland, Claudine, Courage, Carolina, Strozzi, Susi, Tschumi, Sibylle, Gallati, Sabina, and Lemke, Johannes R.
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- 2012
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15. 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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16. 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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17. Lambdoid synostosis and craniofacial dysmorphism with normal intellect: A novel syndrome?
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Rieubland, Claudine, Holmes, Anthony D., Caramins, Melody, Roscioli, Tony, and Amor, David J.
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- 2011
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18. Two cases of trisomy 16 mosaicism ascertained postnatally
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Rieubland, Claudine, Francis, David, Houben, Leonie, Corrie, Sylvea, Bankier, Agnes, and White, Susan M.
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- 2009
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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
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- 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
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- 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. 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, 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
23. 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, Andersen, Janne Bayer, 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., and Rieubland, Claudine
- Subjects
CYTOSKELETAL proteins ,GENOTYPES ,PHENOTYPES ,INTERLEUKIN-33 ,PROTEIN models ,MOLECULAR models - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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24. 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
25. 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
- Published
- 2014
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26. 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, Vink, Arja, Lachaud, Matthias, Joong, Anna, Schott, Jean-Jacques, Horie, Minoru, Denjoy, Isabelle, Crotti, Lia, Shimizu, Wataru, Bos, Johan, Stephenson, Elizabeth, Wong, Leonie, Abrams, Dominic, Davis, Andrew, Winbo, Annika, Dubin, Anne, Sanatani, Shubhayan, Liberman, Leonardo, Kaski, Juan-Pablo, Rudic, Boris, Kwok, Sit Yee, Rieubland, Claudine, Tfelt-Hansen, Jacob, Van Hare, George, Guyomarc’h-Delasalle, Béatrice, Blom, Nico, Wijeyeratne, Yanushi, Gourraud, Jean-Baptiste, Le Marec, Hervé, Ozawa, Junichi, Fressart, Véronique, Lupoglazoff, Jean-Marc, Dagradi, Federica, Spazzolini, Carla, Aiba, Takeshi, Tester, David, Zahavich, Laura, Beauséjour-Ladouceur, Virginie, Jadhav, Mangesh, Skinner, Jonathan, Franciosi, Sonia, Krahn, Andrew, Abdelsayed, Mena, Ruben, Peter, Yung, Tak-Cheung, Ackerman, Michael, Wilde, Arthur, Schwartz, Peter, and Probst, Vincent
- Published
- 2019
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27. Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia
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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
28. Phenotypic and molecular characterization of a novel case of dyssegmental dysplasia, Silverman-Handmaker type
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Rieubland, Claudine, Jacquemont, Sebastien, Mittaz, Laureane, Osterheld, Maria-Chiara, Vial, Yvan, Superti-Furga, Andrea, Unger, Sheila, and Bonafé, Luisa
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- 2010
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29. Uncombable hair syndrome: A clinical report
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Rieubland, Claudine, de Viragh, Pierre A., and Addor, Marie-Claude
- Published
- 2007
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30. Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome: five cases with intragenic mutations or complete deletions of GLI3.
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Hurst, Jane A., Jenkins, Dagan, Vasudevan, Pradeep C., Kirchhoff, Maria, Skovby, Flemming, Rieubland, Claudine, Gallati, Sabina, Rittinger, Olaf, Kroisel, Peter M., Johnson, David, Biesecker, Leslie G., and Wilkie, Andrew OM
- Subjects
CRANIOFACIAL dysostosis ,POLYDACTYLY ,ACROCEPHALOSYNDACTYLIA type II ,MOLECULAR genetics ,CORPUS callosum abnormalities - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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31. Functional characterization of a novel SCN5A variant associated with long QT syndrome and sudden cardiac death
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Neubauer, Jacqueline, Wang, Zizun, Rougier, Jean-Sébastien, Abriel, Hugues, Rieubland, Claudine, Bartholdi, Deborah, Haas, Cordula, and Medeiros-Domingo, Argelia
- Subjects
570 Life sciences ,biology ,610 Medicine & health ,3. Good health - Abstract
Sudden arrhythmic death syndrome (SADS) in young individuals is a devastating and tragic event often caused by an undiagnosed inherited cardiac disease. Although post-mortem genetic testing represents a promising tool to elucidate potential disease-causing mechanisms in such autopsy-negative death cases, a variant interpretation is still challenging, and functional consequences of identified sequence alterations often remain unclear. Recently, we have identified a novel heterozygous missense variant (N1774H) in the Nav1.5 channel-encoding gene SCN5A in a 19-year-old female SADS victim. The aim of this study was to perform a co-segregation analysis in family members of the index case and to evaluate the functional consequences of this SCN5A variant. Functional characterization of the SCN5A N1774H variant was performed using patch-clamp techniques in TsA-201 cell line transiently expressing either wild-type or variant Nav1.5 channels. Electrophysiological analyses revealed that variant Nav1.5 channels show a loss-of-function in the peak current densities, but an increased late current compared to the wild-type channels, which could lead to both, loss- and gain-of-function respectively. Furthermore, clinical assessment and genetic testing of the relatives of the index case showed that all N1774H mutation carriers have prolonged QT intervals. The identification of several genotype and phenotype positive family members and the functional implication of the SCN5A N1774H variant support the evidence of the in silico predicted pathogenicity of the here reported sequence alteration.
32. The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.
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Saffari A, Lau T, Tajsharghi H, Karimiani EG, Kariminejad A, Efthymiou S, Zifarelli G, Sultan T, Toosi MB, Sedighzadeh S, Siu VM, Ortigoza-Escobar JD, AlShamsi AM, Ibrahim S, Al-Sannaa NA, Al-Hertani W, Sandra W, Tarnopolsky M, Alavi S, Li C, Day-Salvatore DL, Martínez-González MJ, Levandoski KM, Bedoukian E, Madan-Khetarpal S, Idleburg MJ, Menezes MJ, Siddharth A, Platzer K, Oppermann H, Smitka M, Collins F, Lek M, Shahrooei M, Ghavideldarestani M, Herman I, Rendu J, Faure J, Baker J, Bhambhani V, Calderwood L, Akhondian J, Imannezhad S, Mirzadeh HS, Hashemi N, Doosti M, Safi M, Ahangari N, Torbati PN, Abedini S, Salpietro V, Gulec EY, Eshaghian S, Ghazavi M, Pascher MT, Vogel M, Abicht A, Moutton S, Bruel AL, Rieubland C, Gallati S, Strom TM, Lochmüller H, Mohammadi MH, Alvi JR, Zackai EH, Keena BA, Skraban CM, Berger SI, Andrew EH, Rahimian E, Morrow MM, Wentzensen IM, Millan F, Henderson LB, Dafsari HS, Jungbluth H, Gomez-Ospina N, McRae A, Peter M, Veltra D, Marinakis NM, Sofocleous C, Ashrafzadeh F, Pehlivan D, Lemke JR, Melki J, Benezit A, Bauer P, Weis D, Lupski JR, Senderek J, Christodoulou J, Chung WK, Goodchild R, Offiah AC, Moreno-De-Luca A, Suri M, Ebrahimi-Fakhari D, Houlden H, and Maroofian R
- Subjects
- Male, Humans, Cross-Sectional Studies, Mutation genetics, Phenotype, Molecular Chaperones genetics, Dystonia genetics, Dystonic Disorders genetics, Nervous System Malformations
- Abstract
In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated with torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with AMC5-TOR1A have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with foetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71%, with higher mortality in males. Death occurred at a median age of 1.2 months (1 week-9 years), due to respiratory failure, cardiac arrest or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2023
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33. Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology.
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Banka S, Bennington A, Baker MJ, Rijckmans E, Clemente GD, Ansor NM, Sito H, Prasad P, Anyane-Yeboa K, Badalato L, Dimitrov B, Fitzpatrick D, Hurst ACE, Jansen AC, Kelly MA, Krantz I, Rieubland C, Ross M, Rudy NL, Sanz J, Stouffs K, Xu ZL, Malliri A, Kazanietz MG, and Millard TH
- Subjects
- Animals, Mice, Neurons, NIH 3T3 Cells, Signal Transduction genetics, Megalencephaly genetics, Neurodevelopmental Disorders genetics, rac1 GTP-Binding Protein
- Abstract
RAC1 is a highly conserved Rho GTPase critical for many cellular and developmental processes. De novo missense RAC1 variants cause a highly variable neurodevelopmental disorder. Some of these variants have previously been shown to have a dominant negative effect. Most previously reported patients with this disorder have either severe microcephaly or severe macrocephaly. Here, we describe eight patients with pathogenic missense RAC1 variants affecting residues between Q61 and R68 within the switch II region of RAC1. These patients display variable combinations of developmental delay, intellectual disability, brain anomalies such as polymicrogyria and cardiovascular defects with normocephaly or relatively milder micro- or macrocephaly. Pulldown assays, NIH3T3 fibroblast spreading assays and staining for activated PAK1/2/3 and WAVE2 suggest that these variants increase RAC1 activity and over-activate downstream signalling targets. Axons of neurons isolated from Drosophila embryos expressing the most common of the activating variants are significantly shorter, with an increased density of filopodial protrusions. In vivo, these embryos exhibit frequent defects in axonal organization. Class IV dendritic arborization neurons expressing this variant exhibit a significant reduction in the total area of the dendritic arbour, increased branching and failure of self-avoidance. RNAi knock down of the WAVE regulatory complex component Cyfip significantly rescues these morphological defects. These results establish that activating substitutions affecting residues Q61-R68 within the switch II region of RAC1 cause a developmental syndrome. Our findings reveal that these variants cause altered downstream signalling, resulting in abnormal neuronal morphology and reveal the WAVE regulatory complex/Arp2/3 pathway as a possible therapeutic target for activating RAC1 variants. These insights also have the potential to inform the mechanism and therapy for other disorders caused by variants in genes encoding other Rho GTPases, their regulators and downstream effectors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2022
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34. SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.
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Baruteau AE, Kyndt F, Behr ER, Vink AS, Lachaud M, Joong A, Schott JJ, Horie M, Denjoy I, Crotti L, Shimizu W, Bos JM, Stephenson EA, Wong L, Abrams DJ, Davis AM, Winbo A, Dubin AM, Sanatani S, Liberman L, Kaski JP, Rudic B, Kwok SY, Rieubland C, Tfelt-Hansen J, Van Hare GF, Guyomarc'h-Delasalle B, Blom NA, Wijeyeratne YD, Gourraud JB, Le Marec H, Ozawa J, Fressart V, Lupoglazoff JM, Dagradi F, Spazzolini C, Aiba T, Tester DJ, Zahavich LA, Beauséjour-Ladouceur V, Jadhav M, Skinner JR, Franciosi S, Krahn AD, Abdelsayed M, Ruben PC, Yung TC, Ackerman MJ, Wilde AA, Schwartz PJ, and Probst V
- Subjects
- Age Factors, Asymptomatic Diseases, Brugada Syndrome genetics, Child, Child, Preschool, Electrocardiography, Female, Follow-Up Studies, Gain of Function Mutation, Humans, Infant, Infant, Newborn, Long QT Syndrome genetics, Loss of Function Mutation, Male, Retrospective Studies, Risk Factors, Cardiac Conduction System Disease genetics, Genetic Association Studies, NAV1.5 Voltage-Gated Sodium Channel genetics
- 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.
- Published
- 2018
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35. Recommendations for genetic testing and counselling after sudden cardiac death: practical aspects for Swiss practice.
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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
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36. Phenotypes and genotypes in individuals with SMC1A variants.
- Author
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Huisman S, Mulder PA, Redeker E, Bader I, Bisgaard AM, Brooks A, Cereda A, Cinca C, Clark D, Cormier-Daire V, Deardorff MA, Diderich K, Elting M, van Essen A, FitzPatrick D, Gervasini C, Gillessen-Kaesbach G, Girisha KM, Hilhorst-Hofstee Y, Hopman S, Horn D, Isrie M, Jansen S, Jespersgaard C, Kaiser FJ, Kaur M, Kleefstra T, Krantz ID, Lakeman P, Landlust A, Lessel D, Michot C, Moss J, Noon SE, Oliver C, Parenti I, Pie J, Ramos FJ, Rieubland C, Russo S, Selicorni A, Tümer Z, Vorstenbosch R, Wenger TL, van Balkom I, Piening S, Wierzba J, and Hennekam RC
- Subjects
- Adolescent, Adult, Child, Child, Preschool, De Lange Syndrome diagnosis, De Lange Syndrome physiopathology, Exome genetics, Humans, Infant, Infant, Newborn, Male, Middle Aged, Netherlands epidemiology, Rett Syndrome diagnosis, Rett Syndrome physiopathology, Spasms, Infantile diagnosis, Spasms, Infantile genetics, Spasms, Infantile physiopathology, Young Adult, Cell Cycle Proteins genetics, Chromosomal Proteins, Non-Histone genetics, De Lange Syndrome genetics, Proteins genetics, Rett Syndrome genetics
- 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., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
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37. Sudden cardiac death in forensic medicine – Swiss recommendations for a multidisciplinary approach.
- Author
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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
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38. Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia.
- Author
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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
39. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas.
- Author
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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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