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187 results on '"Trimouille, Aurélien"'

1. ARF1-related disorder: phenotypic and molecular spectrum.

Author

de Sainte Agathe, Jean-Madeleine, Pode-Shakked, Ben, Naudion, Sophie, Michaud, Vincent, Arveiler, Benoit, Fergelot, Patricia, Delmas, Jean, Keren, Boris, Poirsier, Céline, Alkuraya, Fowzan, Tabarki, Brahim, Bend, Eric, Davis, Kellie, Bebin, Martina, Thompson, Michelle, Bryant, Emily, Wagner, Matias, Hannibal, Iris, Lenberg, Jerica, Krenn, Martin, Wigby, Kristen, Friedman, Jennifer, Iascone, Maria, Cereda, Anna, Miao, Térence, LeGuern, Eric, Sherr, Elliott, Caluseriu, Oana, Tidwell, Timothy, Bayrak-Toydemir, Pinar, Hagedorn, Caroline, Brugger, Melanie, Vill, Katharina, Morneau-Jacob, Francois-Dominique, Chung, Wendy, Weaver, Kathryn, Owens, Joshua, Husami, Ammar, Chaudhari, Bimal, Stone, Brandon, Burns, Katie, Li, Rachel, de Lange, Iris, Biehler, Margaux, Ginglinger, Emmanuelle, Gérard, Bénédicte, Stottmann, Rolf, Trimouille, Aurélien, and Argilli, Emanuela

Subjects
epilepsy, human genetics, sequence analysis, DNA, Humans, Brain, Genotype, Intellectual Disability, Microcephaly, Periventricular Nodular Heterotopia, Phenotype, Seizures
Abstract

PURPOSE: ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of ARF1-related neurodevelopmental disorder. METHODS: We collected detailed phenotypes of an international cohort of individuals (n=17) with ARF1 variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. RESULTS: De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in ARF1 were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. CONCLUSION: We confirm the role of ARF1 in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration.

Published
2023

2. Episignatures in practice: independent evaluation of published episignatures for the molecular diagnostics of ten neurodevelopmental disorders

Author

Husson, Thomas, Lecoquierre, François, Nicolas, Gaël, Richard, Anne-Claire, Afenjar, Alexandra, Audebert-Bellanger, Séverine, Badens, Catherine, Bilan, Frédéric, Bizaoui, Varoona, Boland, Anne, Bonnet-Dupeyron, Marie-Noëlle, Brischoux-Boucher, Elise, Bonnet, Céline, Bournez, Marie, Boute, Odile, Brunelle, Perrine, Caumes, Roseline, Charles, Perrine, Chassaing, Nicolas, Chatron, Nicolas, Cogné, Benjamin, Colin, Estelle, Cormier-Daire, Valérie, Dard, Rodolphe, Dauriat, Benjamin, Delanne, Julian, Deleuze, Jean-François, Demurger, Florence, Denommé-Pichon, Anne-Sophie, Depienne, Christel, Dieux, Anne, Dubourg, Christèle, Edery, Patrick, El Chehadeh, Salima, Faivre, Laurence, Fergelot, Patricia, Fradin, Mélanie, Garde, Aurore, Geneviève, David, Gilbert-Dussardier, Brigitte, Goizet, Cyril, Goldenberg, Alice, Gouy, Evan, Guerrot, Anne-Marie, Guimier, Anne, Harzalla, Inès, Héron, Delphine, Isidor, Bertrand, Lacombe, Didier, Le Guillou Horn, Xavier, Keren, Boris, Kuechler, Alma, Lacaze, Elodie, Lavillaureix, Alinoë, Lehalle, Daphné, Lesca, Gaëtan, Lespinasse, James, Levy, Jonathan, Lyonnet, Stanislas, Morel, Godeliève, Jean-Marçais, Nolwenn, Marlin, Sandrine, Marsili, Luisa, Mignot, Cyril, Nambot, Sophie, Nizon, Mathilde, Olaso, Robert, Pasquier, Laurent, Perrin, Laurine, Petit, Florence, Pingault, Veronique, Piton, Amélie, Prieur, Fabienne, Putoux, Audrey, Planes, Marc, Odent, Sylvie, Quélin, Chloé, Quemener-Redon, Sylvia, Rama, Mélanie, Rio, Marlène, Rossi, Massimiliano, Schaefer, Elise, Rondeau, Sophie, Saugier-Veber, Pascale, Smol, Thomas, Sigaudy, Sabine, Touraine, Renaud, Mau-Them, Frederic Tran, Trimouille, Aurélien, Van Gils, Julien, Vanlerberghe, Clémence, Vantalon, Valérie, Vera, Gabriella, Vincent, Marie, Ziegler, Alban, Guillin, Olivier, Campion, Dominique, and Charbonnier, Camille

Published
2024
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4. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author

Abbott, Kristin M., Banka, Siddharth, de Boer, Elke, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Denommé-Pichon, Anne-Sophie, Faivre, Laurence, Gilissen, Christian, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jackson, Adam, Kerstjens, Mieke, Kleefstra, Tjitske, Martín, Estrella López, Macek, Milan, Jr., Matalonga, Leslie, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Pizzi, Simone, Posada, Manuel, Radio, Francesca C., Renieri, Alessandra, Riess, Olaf, Rooryck, Caroline, Ryba, Lukas, Agathe, Jean-Madeleine de Sainte, Santen, Gijs W.E., Schwarz, Martin, Tartaglia, Marco, Thauvin, Christel, Torella, Annalaura, Trimouille, Aurélien, Verloes, Alain, Vissers, Lisenka, Vitobello, Antonio, Votypka, Pavel, Zguro, Kristina, Boer, Elke de, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B.A.W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Graessner, Holm, Zurek, Birte, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, ‘t Hoen, Peter A.C., Vissers, Lisenka E.L.M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Duffourd, Yannis, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Lišková, Petra, Doležalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Başak, Ayşe Nazlı, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A.L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Radio, Francesca Clementina, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Fallerini, Chiara, Benetti, Elisa, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, Alembik, Yves, Jean-Marçais, Nolwenn, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Safraou, Hana, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, de Vries, Bert B.A., Willemsen, Marjolein H., and Philippe, Christophe

Published
2023
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5. SRSF1 haploinsufficiency is responsible for a syndromic developmental disorder associated with intellectual disability

Author

Bogaert, Elke, Garde, Aurore, Gautier, Thierry, Rooney, Kathleen, Duffourd, Yannis, LeBlanc, Pontus, van Reempts, Emma, Tran Mau-Them, Frederic, Wentzensen, Ingrid M., Au, Kit Sing, Richardson, Kate, Northrup, Hope, Gatinois, Vincent, Geneviève, David, Louie, Raymond J., Lyons, Michael J., Laulund, Lone Walentin, Brasch-Andersen, Charlotte, Maxel Juul, Trine, El It, Fatima, Marle, Nathalie, Callier, Patrick, Relator, Raissa, Haghshenas, Sadegheh, McConkey, Haley, Kerkhof, Jennifer, Cesario, Claudia, Novelli, Antonio, Brunetti-Pierri, Nicola, Pinelli, Michele, Pennamen, Perrine, Naudion, Sophie, Legendre, Marine, Courdier, Cécile, Trimouille, Aurelien, Fenzy, Martine Doco, Pais, Lynn, Yeung, Alison, Nugent, Kimberly, Roeder, Elizabeth R., Mitani, Tadahiro, Posey, Jennifer E., Calame, Daniel, Yonath, Hagith, Rosenfeld, Jill A., Musante, Luciana, Faletra, Flavio, Montanari, Francesca, Sartor, Giovanna, Vancini, Alessandra, Seri, Marco, Besmond, Claude, Poirier, Karine, Hubert, Laurence, Hemelsoet, Dimitri, Munnich, Arnold, Lupski, James R., Philippe, Christophe, Thauvin-Robinet, Christel, Faivre, Laurence, Sadikovic, Bekim, Govin, Jérôme, Dermaut, Bart, and Vitobello, Antonio

Published
2023
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6. Genome-wide variant calling in reanalysis of exome sequencing data uncovered a pathogenic TUBB3 variant

Author

Boer, Elke de, Cohen, Enzo, Cuesta, Isabel, Danis, Daniel, Denommé-Pichon, Anne-Sophie, Gao, Fei, Gilissen, Christian, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Matalonga, Leslie, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, Paske, Iris B.A.W. te, Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, Trimouille, Aurélien, van der Velde, Joeri K., Vandrovcova, Jana, Vitobello, Antonio, Zurek, Birte, Abbot, Kristin M., Banka, Siddharth, Benetti, Elisa, de Boer, Elke, Casari, Giorgio, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Ellwanger, Kornelia, Faivre, Laurence, Graessner, Holm, Haack, Tobias B., Hammarsjö, Anna, Havlovicova, Marketa, Hoischen, Alexander, Hugon, Anne, Jackson, Adam, Kerstjens, Mieke, Kleefstra, Tjitske, Lindstrand, Anna, Martín, Estrella López, Macek, Milan, Jr., Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Nordgren, Ann, Pettersson, Maria, Pinelli, Michele, Pizzi, Simone, Posada, Manuel, Radio, Francesca C., Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Santen, Gijs W.E., Schwarz, Martin, Tartaglia, Marco, Thauvin, Christel, Torella, Annalaura, Verloes, Alain, Vissers, Lisenka, Votypka, Pavel, Vyshka, Klea, Zguro, Kristina, Yaldiz, Burcu, Laurie, Steve, de Reuver, Rick, Kwint, Michael, Pfundt, Rolph, Willemsen, Michèl A.A.P., Vries, Bert B.A. de, Vitobello, A., and Vissers, Lisenka E.L.M.

Published
2022
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8. TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions

Author

Genetica Sectie Genoomdiagnostiek, Child Health, Genetica Klinische Genetica, Circulatory Health, Almousa, Hashem, Lewis, Sara A., Bakhtiari, Somayeh, Nordlie, Sandra Hinz, Pagnozzi, Alex, Magee, Helen, Efthymiou, Stephanie, Heim, Jennifer A., Cornejo, Patricia, Zaki, Maha S., Anwar, Najwa, Maqbool, Shazia, Rahman, Fatima, Neilson, Derek E., Vemuri, Anusha, Jin, Sheng Chih, Yang, Xiao Ru, Heidari, Abolfazl, Van Gassen, Koen, Trimouille, Aurélien, Thauvin-Robinet, Christel, Liu, James, Bruel, Ange Line, Tomoum, Hoda, Shata, Mennatallah O., Hashem, Mais O., Toosi, Mehran Beiraghi, Karimiani, Ehsan Ghayoor, Yeşil, Gözde, Lingappa, Lokesh, Baruah, Debangana, Ebrahimzadeh, Farnoosh, Van-Gils, Julien, Faivre, Laurence, Zamani, Mina, Galehdari, Hamid, Sadeghian, Saeid, Shariati, Gholamreza, Mohammad, Rahema, Van Der Smagt, Jasper, Qari, Alya, Vincent, John B., Innes, A. Micheil, Dursun, Ali, Özgül, R. Köksal, Akar, Halil Tuna, Bilguvar, Kaya, Mignot, Cyril, Keren, Boris, Raveli, Claudia, Burglen, Lydie, Afenjar, Alexandra, Kaat, Laura Donker, Van Slegtenhorst, Marjon, Alkuraya, Fowzan, Houlden, Henry, Padilla-Lopez, Sergio, Maroofian, Reza, Sacher, Michael, Kruer, Michael C., Genetica Sectie Genoomdiagnostiek, Child Health, Genetica Klinische Genetica, Circulatory Health, Almousa, Hashem, Lewis, Sara A., Bakhtiari, Somayeh, Nordlie, Sandra Hinz, Pagnozzi, Alex, Magee, Helen, Efthymiou, Stephanie, Heim, Jennifer A., Cornejo, Patricia, Zaki, Maha S., Anwar, Najwa, Maqbool, Shazia, Rahman, Fatima, Neilson, Derek E., Vemuri, Anusha, Jin, Sheng Chih, Yang, Xiao Ru, Heidari, Abolfazl, Van Gassen, Koen, Trimouille, Aurélien, Thauvin-Robinet, Christel, Liu, James, Bruel, Ange Line, Tomoum, Hoda, Shata, Mennatallah O., Hashem, Mais O., Toosi, Mehran Beiraghi, Karimiani, Ehsan Ghayoor, Yeşil, Gözde, Lingappa, Lokesh, Baruah, Debangana, Ebrahimzadeh, Farnoosh, Van-Gils, Julien, Faivre, Laurence, Zamani, Mina, Galehdari, Hamid, Sadeghian, Saeid, Shariati, Gholamreza, Mohammad, Rahema, Van Der Smagt, Jasper, Qari, Alya, Vincent, John B., Innes, A. Micheil, Dursun, Ali, Özgül, R. Köksal, Akar, Halil Tuna, Bilguvar, Kaya, Mignot, Cyril, Keren, Boris, Raveli, Claudia, Burglen, Lydie, Afenjar, Alexandra, Kaat, Laura Donker, Van Slegtenhorst, Marjon, Alkuraya, Fowzan, Houlden, Henry, Padilla-Lopez, Sergio, Maroofian, Reza, Sacher, Michael, and Kruer, Michael C.

Published
2024

9. Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS):new insights from the fetal perspective

Author

Cuinat, Silvestre, Quélin, Chloé, Effray, Claire, Dubourg, Christèle, Le Bouar, Gwenaelle, Cabaret-Dufour, Anne-Sophie, Loget, Philippe, Proisy, Maia, Sauvestre, Fanny, Sarreau, Mélie, Martin-Berenguer, Sophie, Beneteau, Claire, Naudion, Sophie, Michaud, Vincent, Arveiler, Benoit, Trimouille, Aurélien, Macé, Pierre, Sigaudy, Sabine, Glazunova, Olga, Torrents, Julia, Raymond, Laure, Saint-Frison, Marie-Hélène, Attié-Bitach, Tania, Lefebvre, Mathilde, Capri, Yline, Bourgon, Nicolas, Thauvin-Robinet, Christel, Tran Mau-Them, Frédéric, Bruel, Ange-Line, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Faivre, Laurence, Brehin, Anne-Claire, Goldenberg, Alice, Patrier-Sallebert, Sophie, Perani, Alexandre, Dauriat, Benjamin, Bourthoumieu, Sylvie, Yardin, Catherine, Marquet, Valentine, Barnique, Marion, Fiorenza-Gasq, Maryse, Marey, Isabelle, Tournadre, Danielle, Doumit, Raïa, Nugues, Frédérique, Barakat, Tahsin Stefan, Bustos, Francisco, Jaillard, Sylvie, Launay, Erika, Pasquier, Laurent, Odent, Sylvie, Cuinat, Silvestre, Quélin, Chloé, Effray, Claire, Dubourg, Christèle, Le Bouar, Gwenaelle, Cabaret-Dufour, Anne-Sophie, Loget, Philippe, Proisy, Maia, Sauvestre, Fanny, Sarreau, Mélie, Martin-Berenguer, Sophie, Beneteau, Claire, Naudion, Sophie, Michaud, Vincent, Arveiler, Benoit, Trimouille, Aurélien, Macé, Pierre, Sigaudy, Sabine, Glazunova, Olga, Torrents, Julia, Raymond, Laure, Saint-Frison, Marie-Hélène, Attié-Bitach, Tania, Lefebvre, Mathilde, Capri, Yline, Bourgon, Nicolas, Thauvin-Robinet, Christel, Tran Mau-Them, Frédéric, Bruel, Ange-Line, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Faivre, Laurence, Brehin, Anne-Claire, Goldenberg, Alice, Patrier-Sallebert, Sophie, Perani, Alexandre, Dauriat, Benjamin, Bourthoumieu, Sylvie, Yardin, Catherine, Marquet, Valentine, Barnique, Marion, Fiorenza-Gasq, Maryse, Marey, Isabelle, Tournadre, Danielle, Doumit, Raïa, Nugues, Frédérique, Barakat, Tahsin Stefan, Bustos, Francisco, Jaillard, Sylvie, Launay, Erika, Pasquier, Laurent, and Odent, Sylvie

Abstract

INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described.METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots.CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.

Published
2024

11. BLOC1S5 pathogenic variants cause a new type of Hermansky–Pudlak syndrome

Author

Pennamen, Perrine, Le, Linh, Tingaud-Sequeira, Angèle, Fiore, Mathieu, Bauters, Anne, Van Duong Béatrice, Nguyen, Coste, Valentine, Bordet, Jean-Claude, Plaisant, Claudio, Diallo, Modibo, Michaud, Vincent, Trimouille, Aurélien, Lacombe, Didier, Lasseaux, Eulalie, Delevoye, Cédric, Picard, Fanny Morice, Delobel, Bruno, Marks, Michael S., and Arveiler, Benoit

Published
2020
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13. Mutation on MT-CO2 gene induces mitochondrial disease associated with neurodegeneration and intracerebral iron accumulation (NBIA)

Author

Courtois, Sarah, primary, Angelini, Chloé, additional, M. Durand, Christelle, additional, Dias Amoedo, Nivea, additional, Courreges, Armelle, additional, Dumon, Elodie, additional, Le Quang, Mégane, additional, Goizet, Cyril, additional, Martin-Negrier, Marie-Laure, additional, Rossignol, Rodrigue, additional, Lacombe, Didier, additional, Coupry, Isabelle, additional, and Trimouille, Aurélien, additional

Published
2024
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14. De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy

Author

Nabais Sá, Maria J., Venselaar, Hanka, Wiel, Laurens, Trimouille, Aurélien, Lasseaux, Eulalie, Naudion, Sophie, Lacombe, Didier, Piton, Amélie, Vincent-Delorme, Catherine, Zweier, Christiane, Reis, André, Trollmann, Regina, Ruiz, Anna, Gabau, Elisabeth, Vetro, Annalisa, Guerrini, Renzo, Bakhtiari, Somayeh, Kruer, Michael C., Amor, David J., Cooper, Monica S., Bijlsma, Emilia K., Barakat, Tahsin Stefan, van Dooren, Marieke F., van Slegtenhorst, Marjon, Pfundt, Rolph, Gilissen, Christian, Willemsen, Michèl A., de Vries, Bert B. A., de Brouwer, Arjan P. M., and Koolen, David A.

Published
2020
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16. Histologie et réseaux sociaux

Author

Dubois, Fatéméh, Ambrosetti, Damien, Tosca, Lucie, Baud’huin, Marc, Picart, Thiébaud, Artus, Jérôme, Gallet, Marlène, Egloff, Matthieu, Derangere, Valentin, Trimouille, Aurélien, and Gatinois, Vincent

Published
2024
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17. Homozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia

Author

Barish, Scott, Lin, Sheng-Jia, Maroofian, Reza, Gezdirici, Alper, Alhebby, Hamoud, Trimouille, Aurélien, Biderman Waberski, Marta, Mitani, Tadahiro, Huber, Ilka, Tveten, Kristian, Holla, Øystein L., Busk, Øyvind L., Houlden, Henry, Ghayoor Karimiani, Ehsan, Beiraghi Toosi, Mehran, Shervin Badv, Reza, Najarzadeh Torbati, Paria, Eghbal, Fatemeh, Akhondian, Javad, Al Safar, Ayat, Alswaid, Abdulrahman, Zifarelli, Giovanni, Bauer, Peter, Marafi, Dana, Fatih, Jawid M., Huang, Kevin, Petree, Cassidy, Calame, Daniel G., von der Lippe, Charlotte, Alkuraya, Fowzan S., Wali, Sami, Lupski, James R., Varshney, Gaurav K., Posey, Jennifer E., and Pehlivan, Davut

Published
2024
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20. Episignatures in practice: independent evaluation of published episignatures for the molecular diagnostics of ten neurodevelopmental disorders

Author

Husson, Thomas, primary, Lecoquierre, François, additional, Nicolas, Gaël, additional, Richard, Anne-Claire, additional, Afenjar, Alexandra, additional, Audebert-Bellanger, Séverine, additional, Badens, Catherine, additional, Bilan, Frédéric, additional, Bizaoui, Varoona, additional, Boland, Anne, additional, Bonnet-Dupeyron, Marie-Noëlle, additional, Brischoux-Boucher, Elise, additional, Bonnet, Céline, additional, Bournez, Marie, additional, Boute, Odile, additional, Brunelle, Perrine, additional, Caumes, Roseline, additional, Charles, Perrine, additional, Chassaing, Nicolas, additional, Chatron, Nicolas, additional, Cogné, Benjamin, additional, Colin, Estelle, additional, Cormier-Daire, Valérie, additional, Dard, Rodolphe, additional, Dauriat, Benjamin, additional, Delanne, Julian, additional, Deleuze, Jean-François, additional, Demurger, Florence, additional, Denommé-Pichon, Anne-Sophie, additional, Depienne, Christel, additional, Dieux, Anne, additional, Dubourg, Christèle, additional, Edery, Patrick, additional, El Chehadeh, Salima, additional, Faivre, Laurence, additional, Fergelot, Patricia, additional, Fradin, Mélanie, additional, Garde, Aurore, additional, Geneviève, David, additional, Gilbert-Dussardier, Brigitte, additional, Goizet, Cyril, additional, Goldenberg, Alice, additional, Gouy, Evan, additional, Guerrot, Anne-Marie, additional, Guimier, Anne, additional, Harzalla, Inès, additional, Héron, Delphine, additional, Isidor, Bertrand, additional, Lacombe, Didier, additional, Le Guillou Horn, Xavier, additional, Keren, Boris, additional, Kuechler, Alma, additional, Lacaze, Elodie, additional, Lavillaureix, Alinoë, additional, Lehalle, Daphné, additional, Lesca, Gaëtan, additional, Lespinasse, James, additional, Levy, Jonathan, additional, Lyonnet, Stanislas, additional, Morel, Godeliève, additional, Jean-Marçais, Nolwenn, additional, Marlin, Sandrine, additional, Marsili, Luisa, additional, Mignot, Cyril, additional, Nambot, Sophie, additional, Nizon, Mathilde, additional, Olaso, Robert, additional, Pasquier, Laurent, additional, Perrin, Laurine, additional, Petit, Florence, additional, Pingault, Veronique, additional, Piton, Amélie, additional, Prieur, Fabienne, additional, Putoux, Audrey, additional, Planes, Marc, additional, Odent, Sylvie, additional, Quélin, Chloé, additional, Quemener-Redon, Sylvia, additional, Rama, Mélanie, additional, Rio, Marlène, additional, Rossi, Massimiliano, additional, Schaefer, Elise, additional, Rondeau, Sophie, additional, Saugier-Veber, Pascale, additional, Smol, Thomas, additional, Sigaudy, Sabine, additional, Touraine, Renaud, additional, Mau-Them, Frederic Tran, additional, Trimouille, Aurélien, additional, Van Gils, Julien, additional, Vanlerberghe, Clémence, additional, Vantalon, Valérie, additional, Vera, Gabriella, additional, Vincent, Marie, additional, Ziegler, Alban, additional, Guillin, Olivier, additional, Campion, Dominique, additional, and Charbonnier, Camille, additional

Published
2023
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23. TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions

Author

Almousa, Hashem, primary, Lewis, Sara A, additional, Bakhtiari, Somayeh, additional, Nordlie, Sandra Hinz, additional, Pagnozzi, Alex, additional, Magee, Helen, additional, Efthymiou, Stephanie, additional, Heim, Jennifer A, additional, Cornejo, Patricia, additional, Zaki, Maha S, additional, Anwar, Najwa, additional, Maqbool, Shazia, additional, Rahman, Fatima, additional, Neilson, Derek E, additional, Vemuri, Anusha, additional, Jin, Sheng Chih, additional, Yang, Xiao-Ru, additional, Heidari, Abolfazl, additional, van Gassen, Koen, additional, Trimouille, Aurélien, additional, Thauvin-Robinet, Christel, additional, Liu, James, additional, Bruel, Ange-Line, additional, Tomoum, Hoda, additional, Shata, Mennatallah O, additional, Hashem, Mais O, additional, Toosi, Mehran Beiraghi, additional, Ghayoor Karimiani, Ehsan, additional, Yeşil, Gözde, additional, Lingappa, Lokesh, additional, Baruah, Debangana, additional, Ebrahimzadeh, Farnoosh, additional, Van-Gils, Julien, additional, Faivre, Laurence, additional, Zamani, Mina, additional, Galehdari, Hamid, additional, Sadeghian, Saeid, additional, Shariati, Gholamreza, additional, Mohammad, Rahema, additional, van der Smagt, Jasper, additional, Qari, Alya, additional, Vincent, John B, additional, Innes, A Micheil, additional, Dursun, Ali, additional, Özgül, R Köksal, additional, Akar, Halil Tuna, additional, Bilguvar, Kaya, additional, Mignot, Cyril, additional, Keren, Boris, additional, Raveli, Claudia, additional, Burglen, Lydie, additional, Afenjar, Alexandra, additional, Donker Kaat, Laura, additional, van Slegtenhorst, Marjon, additional, Alkuraya, Fowzan, additional, Houlden, Henry, additional, Padilla-Lopez, Sergio, additional, Maroofian, Reza, additional, Sacher, Michael, additional, and Kruer, Michael C, additional

Published
2023
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25. TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions.

Author

Almousa, Hashem, Lewis, Sara A, Bakhtiari, Somayeh, Nordlie, Sandra Hinz, Pagnozzi, Alex, Magee, Helen, Efthymiou, Stephanie, Heim, Jennifer A, Cornejo, Patricia, Zaki, Maha S, Anwar, Najwa, Maqbool, Shazia, Rahman, Fatima, Neilson, Derek E, Vemuri, Anusha, Jin, Sheng Chih, Yang, Xiao-Ru, Heidari, Abolfazl, Gassen, Koen van, and Trimouille, Aurélien

Subjects
GOLGI apparatus, CORPUS callosum, NERVOUS system, NEURAL development, CARRIER proteins, MOVEMENT disorders, EPILEPSY
Abstract

Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes. We expand on limited prior reports on TRAPPC6B with detailed clinical and neuroradiologic assessments, and studies on mechanisms of disease, and new types of variants. We describe 29 additional patients from 18 independent families with biallelic variants in TRAPPC6B. We identified seven homozygous nonsense (n = 12 patients) and eight canonical splice-site variants (n = 17 patients). In addition, we identified one patient with compound heterozygous splice-site/missense variants with a milder phenotype and one patient with homozygous missense variants. Patients displayed non-progressive microcephaly, global developmental delay/intellectual disability, epilepsy and absent expressive language. Movement disorders including stereotypies, spasticity and dystonia were also observed. Brain imaging revealed reductions in cortex, cerebellum and corpus callosum size with frequent white matter hyperintensity. Volumetric measurements indicated globally diminished volume rather than specific regional losses. We identified a reduced rate of trafficking into the Golgi apparatus and Golgi fragmentation in patient-derived fibroblasts that was rescued by wild-type TRAPPC6B. Molecular studies revealed a weakened interaction between mutant TRAPPC6B (c.454C>T, p.Q152*) and its TRAPP binding partner TRAPPC3. Patient-derived fibroblasts from the TRAPPC6B (c.454C>T, p.Q152*) variant displayed reduced levels of TRAPPC6B as well as other TRAPP II complex-specific members (TRAPPC9 and TRAPPC10). Interestingly, the levels of the TRAPPC6B homologue TRAPPC6A were found to be elevated. Moreover, co-immunoprecipitation experiments showed that TRAPPC6A co-precipitates equally with TRAPP II and TRAPP III, while TRAPPC6B co-precipitates significantly more with TRAPP II, suggesting enrichment of the protein in the TRAPP II complex. This implies that variants in TRAPPC6B may preferentially affect TRAPP II functions compared to TRAPP III functions. Finally, we assessed phenotypes in a Drosophila TRAPPC6B -deficiency model. Neuronal TRAPPC6B knockdown impaired locomotion and led to wing posture defects, supporting a role for TRAPPC6B in neuromotor function. Our findings confirm the association of damaging biallelic TRAPPC6B variants with microcephaly, intellectual disability, language impairments, and epilepsy. A subset of patients also exhibited dystonia and/or spasticity with impaired ambulation. These features overlap with disorders arising from pathogenic variants in other TRAPP subunits, particularly components of the TRAPP II complex. These findings suggest that TRAPPC6B is essential for brain development and function, and TRAPP II complex activity may be particularly relevant for mediating this function. [ABSTRACT FROM AUTHOR]

Published
2024
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26. 19p13 microduplications encompassing NFIX are responsible for intellectual disability, short stature and small head circumference

Author

Trimouille, Aurélien, Houcinat, Nada, Vuillaume, Marie-Laure, Fergelot, Patricia, Boucher, Cécile, Toutain, Jérôme, Caignec, Cédric Le, Vincent, Marie, Nizon, Mathilde, Andrieux, Joris, Vanlerberghe, Clémence, Delobel, Bruno, Duban, Bénédicte, Mansour, Sahar, Baple, Emma, McKeown, Colina, Poke, Gemma, Robertshaw, Kate, Fifield, Eve, Fabretto, Antonella, Pecile, Vanna, Gasparini, Paolo, Carrozzi, Marco, Lacombe, Didier, Arveiler, Benoît, Rooryck, Caroline, and Moutton, Sébastien

Published
2018
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27. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, Alembik, Yves, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Denommé-Pichon, Anne-Sophie, Matalonga, Leslie, de Boer, Elke, Jackson, Adam, Benetti, Elisa, Banka, Siddharth, Bruel, Ange-Line, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Duffourd, Yannis, Ellwanger, Kornelia, Fallerini, Chiara, Gilissen, Christian, Graessner, Holm, Haack, Tobias B., Havlovicova, Marketa, Hoischen, Alexander, Jean-Marçais, Nolwenn, Kleefstra, Tjitske, López-Martín, Estrella, Macek, Milan, Mencarelli, Maria Antonietta, Moutton, Sébastien, Pfundt, Rolph, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Safraou, Hana, Schwarz, Martin, Tartaglia, Marco, Thauvin-Robinet, Christel, Thevenon, Julien, Tran Mau-Them, Frédéric, Trimouille, Aurélien, Votypka, Pavel, de Vries, Bert B. A., Willemsen, Marjolein H., Zurek, Birte, Verloes, Alain, Philippe, Christophe, Abbott, Kristin M., Faivre, Laurence, Kerstjens, Mieke, Martín, Estrella López, Macek Jr., Milan, Maystadt, Isabelle, Morleo, Manuela, Nigro, Vicenzo, Pinelli, Michele, Radio, Francesca C., Riess, Olaf, Agathe, Jean-Madeleine De Sainte, Santen, Gijs W. E., Thauvin, Christel, Torella, Annalaura, Vissers, Lisenka, Vitobello, Antonio, Zguro, Kristina, Boer, Elke De, Cohen, Enzo, Danis, Daniel, Gao, Fei, Horvath, Rita, Johari, Mridul, Johanson, Lennart, Li, Shuang, Morsy, Heba, Nelson, Isabelle, Paramonov, Ida, te Paske, Iris B. A. W., Robinson, Peter, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vandrovcova, Jana, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Schüle, Rebecca, Xu, Jishu, Kessler, Christoph, Wayand, Melanie, Synofzik, Matthis, Wilke, Carlo, Traschütz, Andreas, Schöls, Ludger, Hengel, Holger, Lerche, Holger, Kegele, Josua, Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, `t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Sablauskas, Karolis, de Voer, Richarda M., Kamsteeg, Erik-Jan, van de Warrenburg, Bart, van Os, Nienke, Paske, Iris Te, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Maddi, Vatsalya, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Bettolo, Chiara Marini, Manera, Jordi Diaz, Hambleton, Sophie, Engelhardt, Karin, Alexander, Elizabeth, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Laurie, Steven, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Lagorce, David, Hongnat, Oscar, Chahdil, Maroua, Lebreton, Emeline, Stevanin, Giovanni, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Ben Yaou, Rabah, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Li\vsková, Petra, Dole\vzalová, Pavla, Parkinson, Helen, Keane, Thomas, Freeberg, Mallory, Thomas, Coline, Spalding, Dylan, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Houlden, Henry, Reilly, Mary, Efthymiou, Stephanie, Cali, Elisa, Magrinelli, Francesca, Sisodiya, Sanjay M., Rohrer, Jonathan, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, Timmerman, Vincent, Baets, Jonathan, de Vries, Geert, De Winter, Jonathan, Beijer, Danique, de Jonghe, Peter, Van de Vondel, Liedewei, De Ridder, Willem, Weckhuysen, Sarah, Nigro, Vincenzo, Mutarelli, Margherita, Varavallo, Alessandra, Banfi, Sandro, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Gualandi, Francesca, Bigoni, Stefania, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B., Ruvolo, David, Kerstjens Frederikse, Wilhemina S., Zonneveld-Huijssoon, Eveline, Roelofs-Prins, Dieuwke, van Gijn, Marielle, Köhler, Sebastian, Metcalfe, Alison, Drunat, Séverine, Heron, Delphine, Mignot, Cyril, Keren, Boris, Lacombe, Didier, Trimouille, Aurelien, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Cilio, Maria-Roberta, Carpancea, Evelina, Depondt, Chantal, Lederer, Damien, Sznajer, Yves, Duerinckx, Sarah, Mary, Sandrine, Macaya, Alfons, Cazurro-Gutiérrez, Ana, Pérez-Dueñas, Belén, Munell, Francina, Jarava, Clara Franco, Masó, Laura Batlle, Marcé-Grau, Anna, Colobran, Roger, Hackman, Peter, Udd, Bjarne, Hemelsoet, Dimitri, Dermaut, Bart, Schuermans, Nika, Poppe, Bruce, Verdin, Hannah, Osorio, Andrés Nascimento, Depienne, Christel, Roos, Andreas, Cordts, Isabell, Deschauer, Marcus, Striano, Pasquale, Zara, Federico, Riva, Antonella, Iacomino, Michele, Uva, Paolo, Scala, Marcello, Scudieri, Paolo, Claeys, Kristl, Boztug, Kaan, Haimel, Matthias, W.E, Gijs, Ruivenkamp, Claudia A. L., Natera de Benito, Daniel, Thompson, Rachel, Polavarapu, Kiran, Grimbacher, Bodo, Zaganas, Ioannis, Kokosali, Evgenia, Lambros, Mathioudakis, Evangeliou, Athanasios, Spilioti, Martha, Kapaki, Elisabeth, Bourbouli, Mara, Balicza, Peter, Molnar, Maria Judit, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Delgado, Beatriz Martínez, Alonso García de la Rosa, F. Javier, Schröck, Evelin, Rump, Andreas, Mei, Davide, Vetro, Annalisa, Balestrini, Simona, Guerrini, Renzo, Chinnery, Patrick F., Ratnaike, Thiloka, Schon, Katherine, Maver, Ales, Peterlin, Borut, Münchau, Alexander, Lohmann, Katja, Herzog, Rebecca, Pauly, Martje, May, Patrick, Beeson, David, Cossins, Judith, Furini, Simone, Afenjar, Alexandra, Goldenberg, Alice, Masurel, Alice, Phan, Alice, Dieux-Coeslier, Anne, Fargeot, Anne, Guerrot, Anne-Marie, Toutain, Annick, Molin, Arnaud, Sorlin, Arthur, Putoux, Audrey, Jouret, Béatrice, Laudier, Béatrice, Demeer, Bénédicte, Doray, Bérénice, Bonniaud, Bertille, Isidor, Bertrand, Gilbert-Dussardier, Brigitte, Leheup, Bruno, Reversade, Bruno, Paul, Carle, Vincent-Delorme, Catherine, Neiva, Cecilia, Poirsier, Céline, Quélin, Chloé, Chiaverini, Christine, Coubes, Christine, Francannet, Christine, Colson, Cindy, Desplantes, Claire, Wells, Constance, Goizet, Cyril, Sanlaville, Damien, Amram, Daniel, Lehalle, Daphné, Geneviève, David, Gaillard, Dominique, Zivi, Einat, Sarrazin, Elisabeth, Steichen, Elisabeth, Schaefer, Élise, Lacaze, Elodie, Jacquemin, Emmanuel, Bongers, Ernie, Kilic, Esra, Colin, Estelle, Giuliano, Fabienne, Prieur, Fabienne, Laffargue, Fanny, Morice-Picard, Fanny, Petit, Florence, Cartault, François, Feillet, François, Baujat, Geneviève, Morin, Gilles, Diene, Gwenaëlle, Journel, Hubert, Perthus, Isabelle, Lespinasse, James, Alessandri, Jean-Luc, Amiel, Jeanne, Martinovic, Jelena, Delanne, Julian, Albuisson, Juliette, Lambert, Laëtitia, Perrin, Laurence, Ousager, Lilian Bomme, Van Maldergem, Lionel, Pinson, Lucile, Ruaud, Lyse, Samimi, Mahtab, Bournez, Marie, Bonnet-Dupeyron, Marie Noëlle, Vincent, Marie, Jacquemont, Marie-Line, Cordier-Alex, Marie-Pierre, Gérard-Blanluet, Marion, Willems, Marjolaine, Spodenkiewicz, Marta, Doco-Fenzy, Martine, Rossi, Massimiliano, Renaud, Mathilde, Fradin, Mélanie, Mathieu, Michèle, Holder-Espinasse, Muriel H., Houcinat, Nada, Hanna, Nadine, Leperrier, Nathalie, Chassaing, Nicolas, Philip, Nicole, Boute, Odile, Van Kien, Philippe Khau, Parent, Philippe, Bitoun, Pierre, Sarda, Pierre, Vabres, Pierre, Jouk, Pierre-Simon, Touraine, Renaud, El Chehadeh, Salima, Whalen, Sandra, Marlin, Sandrine, Passemard, Sandrine, Grotto, Sarah, Bellanger, Séverine Audebert, Blesson, Sophie, Nambot, Sophie, Naudion, Sophie, Lyonnet, Stanislas, Odent, Sylvie, Attie-Bitach, Tania, Busa, Tiffany, Drouin-Garraud, Valérie, Layet, Valérie, Bizaoui, Varoona, Cusin, Véronica, Capri, Yline, and Alembik, Yves

Abstract

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock.

Published
2023

29. A Solve-RD ClinVar-based reanalysis of 1,522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author

Denommé-Pichon, Anne-Sophie, primary, Matalonga, Leslie, additional, de Boer, Elke, additional, Jackson, Adam, additional, Benetti, Elisa, additional, Banka, Siddharth, additional, Bruel, Ange-Line, additional, Ciolfi, Andrea, additional, Clayton-Smith, Jill, additional, Dallapiccola, Bruno, additional, Duffourd, Yannis, additional, Ellwanger, Kornelia, additional, Fallerini, Chiara, additional, Gilissen, Christian, additional, Graessner, Holm, additional, Haack, Tobias B., additional, Havlovicova, Marketa, additional, Hoischen, Alexander, additional, Jean-Marçais, Nolwenn, additional, Kleefstra, Tjitske, additional, López-Martín, Estrella, additional, Macek, Milan, additional, Mencarelli, Maria Antonietta, additional, Moutton, Sébastien, additional, Pfundt, Rolph, additional, Pizzi, Simone, additional, Posada, Manuel, additional, Radio, Francesca Clementina, additional, Renieri, Alessandra, additional, Rooryck, Caroline, additional, Ryba, Lukas, additional, Safraou, Hana, additional, Schwarz, Martin, additional, Tartaglia, Marco, additional, Thauvin-Robinet, Christel, additional, Thevenon, Julien, additional, Mau-Them, Frédéric Tran, additional, Trimouille, Aurélien, additional, Votypka, Pavel, additional, de Vries, Bert B.A., additional, Willemsen, Marjolein H., additional, Zurek, Birte, additional, Verloes, Alain, additional, Philippe, Christophe, additional, Vitobello, Antonio, additional, Vissers, Lisenka E.L.M., additional, and Faivre, Laurence, additional

Published
2023
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30. SNV-InDel working group: Results and lessons learned from the analysis of 22,035 exomes and genomes from 6 European reference networks

Author

Matalonga, Leslie, Paramonov, Ida, Steyaert, Wouter, Morsy, Heba, Danis, Daniel, Johanson, Lennart, Ratnaike, Thiloka, Vandrovcova, Jana, Boer, Elke De, Denommé-Pichon, Anne-Sophie, Cohen, Enzo, Fernandez, Marcos, Gao, Fei, Gilissen, Christian, Horvath, Rita, Johari, Mridul, Li, Shuang, Nelson, Isabelle, Paske, Iris B.A.W. Te, Piscia, Davide, Robinson, Peter, Savarese, Marco, Töpf, Ana, Trimouille, Aurélien, Velde, Joeri K. van Der, Vitobello, Antonio, Epicare, ERN, Genturis, ERN, Ithaca, ERN, Euro-NMD, ERN, Rita, ERN, RND, ERN, Hoischen, Alexander, Beltran, Sergi, and Bonne, Gisèle

Subjects
Diagnostic Odyssey, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Published
2023

31. A MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis

Author

de Boer, Elke, Ockeloen, Charlotte W., Matalonga, Leslie, Horvath, Rita, Cohen, Enzo, Cuesta, Isabel, Danis, Daniel, Denommé-Pichon, Anne-Sophie, Duffourd, Yannis, Gilissen, Christian, Johari, Mridul, Laurie, Steven, Li, Shuang, Nelson, Isabelle, Peters, Sophia, Paramonov, Ida, Prasanth, Sivakumar, Robinson, Peter, Sablauskas, Karolis, Savarese, Marco, Steyaert, Wouter, Töpf, Ana, van der Velde, Joeri K., Vitobello, Antonio, Rodenburg, Richard J., Coenen, Marieke J. H., Janssen, Mirian, Henssen, Dylan, Banka, Siddharth, Benetti, Elisa, Casari, Giorgio, Ciolfi, Andrea, Clayton-Smith, Jill, Dallapiccola, Bruno, Ellwanger, Kornelia, Faivre, Laurence, Graessner, Holm, Haack, Tobias B., Hammarsjö, Anna, Havlovicova, Marketa, Hoischen, Alexander, Hugon, Anne, Jackson, Adam, Kleefstra, Tjitske, Lindstrand, Anna, López-Martín, Estrella, Macek, Milan, Morleo, Manuela, Nigro, Vicenzo, Nordgren, Ann, Pettersson, Maria, Pinelli, Michele, Pizzi, Simone, Posada, Manuel, Radio, Francesca Clementina, Renieri, Alessandra, Rooryck, Caroline, Ryba, Lukas, Schwarz, Martin, Tartaglia, Marco, Thauvin, Christel, Torella, Annalaura, Verloes, Alain, Vissers, Lisenka, Votypka, Pavel, Vyshka, Klea, Zurek, Birte, Trimouille, Aurélien, Vissers, Lisenka E. L. M., Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Research Council, Evelyn Trust, Newton Fund, European Project: 825619,AI4EU, Dutch Research Council (Holanda), Medical Research Council (Reino Unido), Lily Foundation, Unión Europea. Comisión Europea. H2020, Ockeloen, Charlotte W [0000-0003-0329-1520], Horvath, Rita [0000-0002-9841-170X], Rodenburg, Richard J [0000-0001-5227-3527], Gilissen, Christian [0000-0003-1693-9699], Steyaert, Wouter [0000-0001-8393-0788], Trimouille, Aurélien [0000-0002-3457-5684], Verloes, Alain [0000-0003-4819-0264], Vissers, Lisenka ELM [0000-0001-6470-5497], Apollo - University of Cambridge Repository, de Boer, E., Ockeloen, C. W., Matalonga, L., Horvath, R., Rodenburg, R. J., Coenen, M. J. H., Janssen, M., Henssen, D., Gilissen, C., Steyaert, W., Paramonov, I., Trimouille, A., Kleefstra, T., Verloes, A., Vissers, L. E. L. M., Nigro, V., Torella, A., and Banfi, S.

Subjects
Male, Proband, Mitochondrial DNA, RNA, Transfer, Leu, Brief Communication, Quadriplegia, Whole Exome Sequencing, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Young Adult, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Intellectual Disability, Exome Sequencing, Genetics research, Intellectual disability, Genetics, medicine, Humans, Genetics (clinical), Exome sequencing, 0303 health sciences, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Neurodevelopmental disorders, 030305 genetics & heredity, Correction, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Translational research, medicine.disease, Heteroplasmy, 3. Good health, MT-TL1, Mutation, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Spastic tetraparesis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Neurological disorders, 030217 neurology & neurosurgery
Abstract

Correction: A MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis. Eur J Hum Genet. 2021 Sep;29(9):1470-1471. doi: 10.1038/s41431-021-00937-3. The genetic etiology of intellectual disability remains elusive in almost half of all affected individuals. Within the Solve-RD consortium, systematic re-analysis of whole exome sequencing (WES) data from unresolved cases with (syndromic) intellectual disability (n = 1,472 probands) was performed. This re-analysis included variant calling of mitochondrial DNA (mtDNA) variants, although mtDNA is not specifically targeted in WES. We identified a functionally relevant mtDNA variant in MT-TL1 (NC_012920.1:m.3291T > C; NC_012920.1:n.62T > C), at a heteroplasmy level of 22% in whole blood, in a 23-year-old male with severe intellectual disability, epilepsy, episodic headaches with emesis, spastic tetraparesis, brain abnormalities, and feeding difficulties. Targeted validation in blood and urine supported pathogenicity, with heteroplasmy levels of 23% and 58% in index, and 4% and 17% in mother, respectively. Interestingly, not all phenotypic features observed in the index have been previously linked to this MT-TL1 variant, suggesting either broadening of the m.3291T > C-associated phenotype, or presence of a co-occurring disorder. Hence, our case highlights the importance of underappreciated mtDNA variants identifiable from WES data, especially for cases with atypical mitochondrial phenotypes and their relatives in the maternal line. This work was financially supported by Aspasia grants of the Dutch Research Council (015.014.036 to TK and 015.014.066 to LELMV), the European Research Council (ERC to RH), the Well come Investigator Award (109915/Z/15/Z to RH), the Medical Research Council UK (MR/N025431/1 to RH), the Newton Fund (MR/N027302/1 to RH), the Lily Foundation (RH), and the Evelyn Trust (RH). The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 779257. Sí

Published
2021
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32. First clinical description of a pedigree with complete NAF1 deletion

Author

Galtier, Jean, primary, Dimicoli-Salazar, Sophie, additional, Trimouille, Aurélien, additional, Lainey, Elodie, additional, Revy, Patrick, additional, Bidet, Audrey, additional, Vial, Yoann, additional, Forcade, Edouard, additional, Negrier-Leibreich, Marie-Laure, additional, Rivière, Etienne, additional, Tinat, Julie, additional, Le Meur, Nathalie, additional, Ménard, Christelle, additional, Pigneux, Arnaud, additional, Leguay, Thibaut, additional, Dumas, Pierre-Yves, additional, Ibrahima, Ba, additional, and Kannengiesser, Caroline, additional

Published
2022
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34. Hemidystonia with polymicrogyria is part of ATP1A3-related disorders

Author

Lacombe, Didier, primary, Van-Gils, Julien, additional, Lebrun, Marine, additional, Trimouille, Aurélien, additional, Michaud, Vincent, additional, Cabet, Sara, additional, Chateil, Jean-François, additional, Pedespan, Jean-Michel, additional, Bar, Claire, additional, and Lesca, Gaetan, additional

Published
2022
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35. De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability

Author

Genetica Sectie Genoomdiagnostiek, Child Health, Schalk, Audrey, Cousin, Margot A, Dsouza, Nikita R, Challman, Thomas D, Wain, Karen E, Powis, Zoe, Minks, Kelly, Trimouille, Aurélien, Lasseaux, Eulalie, Lacombe, Didier, Angelini, Chloé, Michaud, Vincent, Van-Gils, Julien, Spataro, Nino, Ruiz, Anna, Gabau, Elizabeth, Stolerman, Elliot, Washington, Camerun, Louie, Ray, Lanpher, Brendan C, Kemppainen, Jennifer L, Innes, Micheil, Kooy, Frank, Meuwissen, Marije, Goldenberg, Alice, Lecoquierre, Francois, Vera, Gabriella, Diderich, Karin E M, Sheidley, Beth, El Achkar, Christelle Moufawad, Park, Meredith, Hamdan, Fadi F, Michaud, Jacques L, Lewis, Ann J, Zweier, Christiane, Reis, André, Wagner, Matias, Weigand, Heike, Journel, Hubert, Keren, Boris, Passemard, Sandrine, Mignot, Cyril, van Gassen, Koen, Brilstra, Eva H, Itzikowitz, Gina, O'Heir, Emily, Allen, Jake, Donald, Kirsten A, Korf, Bruce Richard, Skelton, Tammi, Thompson, Michelle, Robin, Nathaniel H, Rudy, Natasha L, Dobyns, William B, Foss, Kimberly, Zarate, Yuri Alexander, Bosanko, Katherine A, Alembik, Yves, Durand, Benjamin, Tran Mau-Them, Frederic, Ranza, Emmanuelle, Blanc, Xavier, Antonarakis, Stylianos E, McWalter, Kirsty, Torti, Erin, Millan, Francisca, Dameron, Amy, Tokita, Mari, Zimmermann, Michael T, Klee, Eric W, Piton, Amelie, Gerard, Benedicte, Genetica Sectie Genoomdiagnostiek, Child Health, Schalk, Audrey, Cousin, Margot A, Dsouza, Nikita R, Challman, Thomas D, Wain, Karen E, Powis, Zoe, Minks, Kelly, Trimouille, Aurélien, Lasseaux, Eulalie, Lacombe, Didier, Angelini, Chloé, Michaud, Vincent, Van-Gils, Julien, Spataro, Nino, Ruiz, Anna, Gabau, Elizabeth, Stolerman, Elliot, Washington, Camerun, Louie, Ray, Lanpher, Brendan C, Kemppainen, Jennifer L, Innes, Micheil, Kooy, Frank, Meuwissen, Marije, Goldenberg, Alice, Lecoquierre, Francois, Vera, Gabriella, Diderich, Karin E M, Sheidley, Beth, El Achkar, Christelle Moufawad, Park, Meredith, Hamdan, Fadi F, Michaud, Jacques L, Lewis, Ann J, Zweier, Christiane, Reis, André, Wagner, Matias, Weigand, Heike, Journel, Hubert, Keren, Boris, Passemard, Sandrine, Mignot, Cyril, van Gassen, Koen, Brilstra, Eva H, Itzikowitz, Gina, O'Heir, Emily, Allen, Jake, Donald, Kirsten A, Korf, Bruce Richard, Skelton, Tammi, Thompson, Michelle, Robin, Nathaniel H, Rudy, Natasha L, Dobyns, William B, Foss, Kimberly, Zarate, Yuri Alexander, Bosanko, Katherine A, Alembik, Yves, Durand, Benjamin, Tran Mau-Them, Frederic, Ranza, Emmanuelle, Blanc, Xavier, Antonarakis, Stylianos E, McWalter, Kirsty, Torti, Erin, Millan, Francisca, Dameron, Amy, Tokita, Mari, Zimmermann, Michael T, Klee, Eric W, Piton, Amelie, and Gerard, Benedicte

Published
2022

36. De novo variants in ATP2B1 lead to neurodevelopmental delay

Author

Rahimi, Meer Jacob, primary, Urban, Nicole, additional, Wegler, Meret, additional, Sticht, Heinrich, additional, Schaefer, Michael, additional, Popp, Bernt, additional, Gaunitz, Frank, additional, Morleo, Manuela, additional, Nigro, Vincenzo, additional, Maitz, Silvia, additional, Mancini, Grazia M.S., additional, Ruivenkamp, Claudia, additional, Suk, Eun-Kyung, additional, Bartolomaeus, Tobias, additional, Merkenschlager, Andreas, additional, Koboldt, Daniel, additional, Bartholomew, Dennis, additional, Stegmann, Alexander P.A., additional, Sinnema, Margje, additional, Duynisveld, Irma, additional, Salvarinova, Ramona, additional, Race, Simone, additional, de Vries, Bert B.A., additional, Trimouille, Aurélien, additional, Naudion, Sophie, additional, Marom, Daphna, additional, Hamiel, Uri, additional, Henig, Noa, additional, Demurger, Florence, additional, Rahner, Nils, additional, Bartels, Enrika, additional, Hamm, J. Austin, additional, Putnam, Abbey M., additional, Person, Richard, additional, Abou Jamra, Rami, additional, and Oppermann, Henry, additional

Published
2022
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38. First clinical description of a pedigree with complete NAF1 deletion.

Author

Galtier, Jean, Dimicoli-Salazar, Sophie, Trimouille, Aurélien, Lainey, Elodie, Revy, Patrick, Bidet, Audrey, Vial, Yoann, Forcade, Edouard, Negrier-Leibreich, Marie-Laure, Rivière, Etienne, Tinat, Julie, Le Meur, Nathalie, Ménard, Christelle, Pigneux, Arnaud, Leguay, Thibaut, Dumas, Pierre-Yves, Ibrahima, Ba, and Kannengiesser, Caroline

Subjects
DERMATOMYOSITIS, BLOOD diseases, MYOSITIS, INCLUSION body myositis, NUCLEOTIDE sequencing, TANDEM repeats, MEDICAL genetics
Abstract

NGS of genes associated with TBD or inherited aplastic anemia revealed a heterozygous deletion of the I NAF1 i gene in leucocytes DNA, confirmed in buccal swab and hair bulb. Telomeres are tandem repeats of nucleotide sequences at the end of chromosomes which protect DNA from degradation, repair mechanisms and fusion [[1]]. Around thirty per cent of familial PF patients are carriers of a heterozygous pathogenic variation in a telomere maintenance gene [[7]]. Loss-of-function pathogenic variations of genes implicated in telomere maintenance are associated with shortened telomeres leading to clinical and biological consequences named "telomere biology disorder" (TBD). [Extracted from the article]

Published
2023
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39. Renal involvement is frequent in adults with primary mitochondrial disorders: an observational study.

Author

Bakis, Hugo, Trimouille, Aurélien, Vermorel, Agathe, Goizet, Cyril, Belaroussi, Yaniss, Schutz, Sacha, Solé, Guilhem, Combe, Christian, Martin-Negrier, Marie-Laure, and Rigothier, Claire

Subjects
*MITOCHONDRIAL pathology, *KIDNEY glomerulus diseases, *NUCLEAR DNA, *MITOCHONDRIAL DNA, *ADULTS
Abstract

Background Mitochondrial functions are controlled by genes of both mitochondrial and nuclear DNA. Pathogenic variants affecting any of these are responsible for primary mitochondrial disorders (MIDs), which can be diagnosed during adulthood. Kidney functions are highly dependent on mitochondrial respiration. However, the prevalence of MID-associated nephropathies (MIDANs) is unknown in the adult population. We aimed to address this point and to provide a full characterization of MIDANs in this population. Methods We retrospectively included for observational study adults (≥16 years of age) with genetically diagnosed MID between 2000 and 2020 in our tertiary care academic centre when they had a chronic kidney disease (CKD) evaluation. MIDANs were ascertained by CKD occurring in MIDs. The phenotypic, biological, histopathological and genotypic characteristics were recorded from the medical charts. Results We included 80 MID-affected adults and ascertained MIDANs in 28/80 (35%). Kidney diseases under the care of a nephrologist occurred in only 14/28 (50%) of the adults with MIDAN. MIDANs were tubulointerstitial nephropathy in 14/28 patients (50%) and glomerular diseases in 9/28 (32.1%). In adults with MID, MIDAN was negatively associated with higher albumin levels {odds ratio [OR] 0.79 [95% confidence interval (CI) 0.67–0.95]} and vision abnormalities [OR 0.17 (95% CI 0.03–0.94)] and positively associated with hypertension [OR 4.23 (95% CI 1.04–17.17)]. Conclusion MIDANs are frequent among adult MIDs. They are mostly represented by tubulointerstitial nephropathy or glomerular disease. Vision abnormalities, hypertension and albumin levels were independently associated with MIDANs. Our results pave the way for prospective studies investigating the prevalence of MIDANs among undetermined kidney disease populations. [ABSTRACT FROM AUTHOR]

Published
2023
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40. De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability

Author

Schalk, Audrey, primary, Cousin, Margot A, additional, Dsouza, Nikita R, additional, Challman, Thomas D, additional, Wain, Karen E, additional, Powis, Zoe, additional, Minks, Kelly, additional, Trimouille, Aurélien, additional, Lasseaux, Eulalie, additional, Lacombe, Didier, additional, Angelini, Chloé, additional, Michaud, Vincent, additional, Van-Gils, Julien, additional, Spataro, Nino, additional, Ruiz, Anna, additional, Gabau, Elizabeth, additional, Stolerman, Elliot, additional, Washington, Camerun, additional, Louie, Ray, additional, Lanpher, Brendan C, additional, Kemppainen, Jennifer L, additional, Innes, Micheil, additional, Kooy, Frank, additional, Meuwissen, Marije, additional, Goldenberg, Alice, additional, Lecoquierre, Francois, additional, Vera, Gabriella, additional, Diderich, Karin E M, additional, Sheidley, Beth, additional, El Achkar, Christelle Moufawad, additional, Park, Meredith, additional, Hamdan, Fadi F, additional, Michaud, Jacques L, additional, Lewis, Ann J, additional, Zweier, Christiane, additional, Reis, André, additional, Wagner, Matias, additional, Weigand, Heike, additional, Journel, Hubert, additional, Keren, Boris, additional, Passemard, Sandrine, additional, Mignot, Cyril, additional, van Gassen, Koen, additional, Brilstra, Eva H, additional, Itzikowitz, Gina, additional, O'Heir, Emily, additional, Allen, Jake, additional, Donald, Kirsten A, additional, Korf, Bruce Richard, additional, Skelton, Tammi, additional, Thompson, Michelle, additional, Robin, Nathaniel H, additional, Rudy, Natasha L, additional, Dobyns, William B, additional, Foss, Kimberly, additional, Zarate, Yuri Alexander, additional, Bosanko, Katherine A, additional, Alembik, Yves, additional, Durand, Benjamin, additional, Tran Mau-them, Frederic, additional, Ranza, Emmanuelle, additional, Blanc, Xavier, additional, Antonarakis, Stylianos E, additional, McWalter, Kirsty, additional, Torti, Erin, additional, Millan, Francisca, additional, Dameron, Amy, additional, Tokita, Mari, additional, Zimmermann, Michael T, additional, Klee, Eric W, additional, Piton, Amelie, additional, and Gerard, Benedicte, additional

Published
2021
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41. De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability.

Author

Schalk, Audrey, Cousin, Margot A., Dsouza, Nikita R., Challman, Thomas D., Wain, Karen E., Powis, Zoe, Minks, Kelly, Trimouille, Aurélien, Lasseaux, Eulalie, Lacombe, Didier, Angelini, Chloé, Michaud, Vincent, Van-Gils, Julien, Spataro, Nino, Ruiz, Anna, Gabau, Elizabeth, Stolerman, Elliot, Washington, Camerun, Louie, Ray, and Lanpher, Brendan C.

Abstract

Background High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD). Methods This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous AGO1 coding variants, occurring de novo for all those whose transmission could have been verified (26/28). Results A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in- frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues. Recurrently identified variants were present in several unrelated individuals: p.(Phe180del), p.(Leu190Pro), p.(Leu190Arg), p.(Gly199Ser), p.(Val254Ile) and p.(Glu376del). AGO1 encodes the Argonaute 1 protein, which functions in gene- silencing pathways mediated by small non- coding RNAs. Three- dimensional protein structure predictions suggest that these variants might alter the flexibility of the AGO1 linker domains, which likely would impair its function in mRNA processing. Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behaviour and additional behavioural manifestation Conclusion Our study establishes that de novo coding variants in AGO1 are involved in a novel monogenic form of NDD, highly similar to the recently reported AGO2-related NDD. [ABSTRACT FROM AUTHOR]

Published
2022
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42. Implication of folate deficiency in CYP2U1 loss of function

Author

Pujol, Claire, primary, Legrand, Anne, additional, Parodi, Livia, additional, Thomas, Priscilla, additional, Mochel, Fanny, additional, Saracino, Dario, additional, Coarelli, Giulia, additional, Croon, Marijana, additional, Popovic, Milica, additional, Valet, Manon, additional, Villain, Nicolas, additional, Elshafie, Shahira, additional, Issa, Mahmoud, additional, Zuily, Stephane, additional, Renaud, Mathilde, additional, Marelli-Tosi, Cécilia, additional, Legendre, Marine, additional, Trimouille, Aurélien, additional, Kemlin, Isabelle, additional, Mathieu, Sophie, additional, Gleeson, Joseph G., additional, Lamari, Foudil, additional, Galatolo, Daniele, additional, Alkouri, Rana, additional, Tse, Chantal, additional, Rodriguez, Diana, additional, Ewenczyk, Claire, additional, Fellmann, Florence, additional, Kuntzer, Thierry, additional, Blond, Emilie, additional, El Hachimi, Khalid H., additional, Darios, Frédéric, additional, Seyer, Alexandre, additional, Gazi, Anastasia D., additional, Giavalisco, Patrick, additional, Perin, Silvina, additional, Boucher, Jean-Luc, additional, Le Corre, Laurent, additional, Santorelli, Filippo M., additional, Goizet, Cyril, additional, Zaki, Maha S., additional, Picaud, Serge, additional, Mourier, Arnaud, additional, Steculorum, Sophie Marie, additional, Mignot, Cyril, additional, Durr, Alexandra, additional, Trifunovic, Aleksandra, additional, and Stevanin, Giovanni, additional

Published
2021
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43. Solving patients with rare diseases through programmatic reanalysis of genome-phenome data

Author

Matalonga, Leslie, Hernández-Ferrer, Carles, DITF-ITHACA, Solve-RD, Verloes, Alain, Vissers, Lisenka, Vitobello, Antonio, Votypka, Pavel, Vyshka, Klea, Zurek, Birte, Baets, Jonathan, Beijer, Danique, Bonne, Gisèle, Cohen, Enzo, DITF-euroNMD, Solve-RD, Cossins, Judith, Evangelista, Teresinha, Ferlini, Alessandra, Hackman, Peter, Hanna, Michael G, Horvath, Rita, Houlden, Henry, Johari, Mridul, Lau, Jarred, Lochmüller, Hanns, DITF-RND, Solve-RD, Macken, William L, Musacchia, Francesco, Nascimento, Andres, Natera-de Benito, Daniel, Nigro, Vincenzo, Piluso, Giulio, Pini, Veronica, Pitceathly, Robert D S, Polavarapu, Kiran, Cruz, Pedro M Rodriguez, Tonda, Raul, Sarkozy, Anna, Savarese, Marco, Selvatici, Rita, Thompson, Rachel, Udd, Bjarne, Van de Vondel, Liedewei, Vandrovcova, Jana, Zaharieva, Irina, Balicza, Peter, Laurie, Steven, Chinnery, Patrick, Dürr, Alexandra, Haack, Tobias, Hengel, Holger, Kamsteeg, Erik-Jan, Kamsteeg, Christoph, Lohmann, Katja, Macaya, Alfons, Marcé-Grau, Anna, Fernandez-Callejo, Marcos, Maver, Ales, Molnar, Judit, Münchau, Alexander, Peterlin, Borut, Riess, Olaf, Schöls, Ludger, Schüle-Freyer, Rebecca, Stevanin, Giovanni, Synofzik, Matthis, Timmerman, Vincent, Picó, Daniel, van de Warrenburg, Bart, van Os, Nienke, Wayand, Melanie, Wilke, Carlo, Haack, Tobias B, Graessner, Holm, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Garcia-Linares, Carles, Sturm, Marc, Schulze-Hentrich, Julia M, Kessler, Christoph, Heutink, Peter, Brunner, Han, Scheffer, Hans, Papakonstantinou, Anastasios, Hoogerbrugge, Nicoline, 't Hoen, Peter A C, Steyaert, Wouter, Sablauskas, Karolis, Te Paske, Iris, Janssen, Erik, Steehouwer, Marloes, Yaldiz, Burcu, Corvó, Alberto, Brookes, Anthony J, Veal, Colin, Gibson, Spencer, Wadsley, Marc, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Straub, Volker, Piscia, Davide, Joshi, Ricky, Bettolo, Chiara Marini, Specht, Sabine, Clayton-Smith, Jill, Banka, Siddharth, Alexander, Elizabeth, Jackson, Adam, Faivre, Laurence, Thauvin, Christel, Duffourd, Yannis, Tisserant, Emilie, Diez, Hector, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Beltran, Sergi, Gut, Ivo Glynne, Bullich, Gemma, Gut, Ivo, Corvo, Alberto, Garcia, Carles, Hernández, Carles, Paramonov, Ida, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hoischen, Alexander, Hanauer, Marc, Olry, Annie, Lagorce, David, Havrylenko, Svitlana, Izem, Katia, Rigour, Fanny, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Allamand, Valérie, Nelson, Isabelle, Yaou, Rabah Ben, Metay, Corinne, Eymard, Bruno, Atalaia, Antonio, Stojkovic, Tanya, Macek, Milan, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Kremlik, Vlastimil, Parkinson, Helen, Keane, Thomas, Consortia, Solve-RD, Spalding, Dylan, Senf, Alexander, Danis, Daniel, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Reilly, Mary, Muntoni, Francesco, de Jonghe, Peter, Banfi, Sandro, Torella, Annalaura, Cuesta, Isabel, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A, Johansson, Lennart, van der Vries, Gerben, Neerincx, Pieter B, group, Solve-RD SNV-indel working, Denommé-Pichon, Anne-Sophie, Roelofs-Prins, Dieuwke, Köhler, Sebastian, Metcalfe, Alison, Rooryck, Caroline, Trimouille, Aurelien, Castello, Raffaele, Morleo, Manuela, Varavallo, Alessandra, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Martín, Estrella López, Delgado, Beatriz Martínez, de la Rosa, F Javier Alonso García, Radio, Francesca Clementina, Tartaglia, Marco, Renieri, Alessandra, Benetti, Elisa, Molnar, Maria Judit, Gilissen, Christian, Herzog, Rebecca, Pauly, Martje, Osorio, Andres Nascimiento, de Benito, Daniel Natera, Beeson, David, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Schröck, Evelin, Rump, Andreas, Li, Shuang, Prasanth, Sivakumar, Robinson, Peter, van der Velde, Joeri K, de Voer, Richarda M, Evans, Gareth, Sommer, Anna Katharina, Töpf, Ana, Paske, Iris Te, Tischkowitz, Marc, Casari, Giorgio, Ciolfi, Andrea, Dallapiccola, Bruno, de Boer, Elke, Vissers, Lisenka E L M, Hammarsjö, Anna, Havlovicova, Marketa, Hugon, Anne, de Voer, Richarda, Kleefstra, Tjitske, Lindstrand, Anna, López-Martín, Estrella, Nigro, Vicenzo, Nordgren, Ann, Pettersson, Maria, Pinelli, Michele, Pizzi, Simone, DITF-GENTURIS, Solve-RD, Posada, Manuel, Ryba, Lukas, Schwarz, Martin, Trimouille, Aurélien, Solve RD SNV Indel Working Grp, Solve RD DITF GENTURIS, Solve RD DITF ITHACA, Solve RD DITF-euroNMD, Solve RD DITF RND, Solve RD Consortia, Matalonga, L., Hernandez-Ferrer, C., Piscia, D., Cohen, E., Cuesta, I., Danis, D., Denomme-Pichon, A. -S., Duffourd, Y., Gilissen, C., Johari, M., Laurie, S., Li, S., Nelson, I., Peters, S., Paramonov, I., Prasanth, S., Robinson, P., Sablauskas, K., Savarese, M., Steyaert, W., van der Velde, J. K., Vitobello, A., Schule, R., Synofzik, M., Topf, A., Vissers, L. E. L. M., de Voer, R., Aretz, S., Capella, G., de Voer, R. M., Evans, G., Pelaez, J. G., Holinski-Feder, E., Hoogerbrugge, N., Laner, A., Oliveira, C., Rump, A., Schrock, E., Sommer, A. K., Steinke-Lange, V., Paske, I., Tischkowitz, M., Valle, L., Banka, S., Benetti, E., Casari, G., Ciolfi, A., Clayton-Smith, J., Dallapiccola, B., de Boer, E., Ellwanger, K., Faivre, L., Graessner, H., Haack, T. B., Hammarsjo, A., Havlovicova, M., Hoischen, A., Hugon, A., Jackson, A., Kleefstra, T., Lindstrand, A., Lopez-Martin, E., Macek, M., Morleo, M., Nigro, V., Nordgren, A., Pettersson, M., Pinelli, M., Pizzi, S., Posada, M., Radio, F. C., Renieri, A., Rooryck, C., Ryba, L., Schwarz, M., Tartaglia, M., Thauvin, C., Torella, A., Trimouille, A., Verloes, A., Vissers, L., Votypka, P., Vyshka, K., Zurek, B., Baets, J., Beijer, D., Bonne, G., Cossins, J., Evangelista, T., Ferlini, A., Hackman, P., Hanna, M. G., Horvath, R., Houlden, H., Lau, J., Lochmuller, H., Macken, W. L., Musacchia, F., Nascimento, A., Natera-de Benito, D., Piluso, G., Pini, V., Pitceathly, R. D. S., Polavarapu, K., Cruz, P. M. R., Sarkozy, A., Selvatici, R., Thompson, R., Udd, B., Van de Vondel, L., Vandrovcova, J., Zaharieva, I., Balicza, P., Chinnery, P., Durr, A., Haack, T., Hengel, H., Kamsteeg, E. -J., Kamsteeg, C., Lohmann, K., Macaya, A., Marce-Grau, A., Maver, A., Molnar, J., Munchau, A., Peterlin, B., Riess, O., Schols, L., Schule-Freyer, R., Stevanin, G., Timmerman, V., van de Warrenburg, B., van Os, N., Wayand, M., Wilke, C., Tonda, R., Fernandez-Callejo, M., Pico, D., Garcia-Linares, C., Papakonstantinou, A., Corvo, A., Joshi, R., Diez, H., Gut, I., Beltran, S., Ossowski, S., Demidov, G., Sturm, M., Schulze-Hentrich, J. M., Kessler, C., Heutink, P., Brunner, H., Scheffer, H., 't Hoen, P. A. C., te Paske, I., Janssen, E., Steehouwer, M., Yaldiz, B., Brookes, A. J., Veal, C., Gibson, S., Wadsley, M., Mehtarizadeh, M., Riaz, U., Warren, G., Dizjikan, F. Y., Shorter, T., Straub, V., Bettolo, C. M., Specht, S., Alexander, E., Tisserant, E., Bruel, A. -L., Peyron, C., Pelissier, A., Gut, I. G., Bullich, G., Garcia, C., Hernandez, C., Gumus, G., Bros-Facer, V., Rath, A., Hanauer, M., Olry, A., Lagorce, D., Havrylenko, S., Izem, K., Rigour, F., Davoine, C. -S., Guillot-Noel, L., Heinzmann, A., Coarelli, G., Allamand, V., Yaou, R. B., Metay, C., Eymard, B., Atalaia, A., Stojkovic, T., Turnovec, M., Thomasova, D., Kremlikova, R. P., Frankova, V., Kremlik, V., Parkinson, H., Keane, T., Spalding, D., Senf, A., Robert, G., Costa, A., Patch, C., Hanna, M., Reilly, M., Muntoni, F., de Jonghe, P., Banfi, S., Rossi, R., Neri, M., Spier, I., Matos, A. R., Jose, C. S., Ferreira, M., Gullo, I., Fernandes, S., Garrido, L., Ferreira, P., Carneiro, F., Swertz, M. A., Johansson, L., van der Vries, G., Neerincx, P. B., Roelofs-Prins, D., Kohler, S., Metcalfe, A., Castello, R., Varavallo, A., De la Paz, M. P., Sanchez, E. B., Martin, E. L., Delgado, B. M., de la Rosa, F. J. A. G., Molnar, M. J., Herzog, R., Pauly, M., Osorio, A. N., de Benito, D. N., Beeson, D., Unión Europea. Comisión Europea. H2020, Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España), Government of Catalonia (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Instituto Nacional de Bioinformatica (España), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Instituto de Salud Carlos III [Madrid] (ISC), Radboud University Medical Center [Nijmegen], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Equipe GAD (LNC - U1231), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Barcelona Institute of Science and Technology (BIST), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Myologie, University of Helsinki, Department of Medical and Clinical Genetics, Medicum, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Genetic testing, Computer science, genetics [Rare Diseases], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], EXOME, MEDICAL GENETICS, Diseases, Disease, VARIANTS, Genome informatics, Genomic analysis, Diseases, Genetic testing, Genome informatics, Genomic analysis, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Exome, Genetics (clinical), Exome sequencing, 0303 health sciences, Application programming interface, methods [Genomics], 030305 genetics & heredity, 1184 Genetics, developmental biology, physiology, Genomics, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Pedigree, diagnosis [Rare Diseases], Chemistry, Medical genetics, medicine.medical_specialty, methods [Genetic Testing], MEDLINE, Socio-culturale, Phenome, AMERICAN-COLLEGE, INHERITANCE, Sensitivity and Specificity, Article, standards [Genetic Testing], 03 medical and health sciences, Rare Diseases, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Genetics, medicine, Humans, ddc:610, Genetic Testing, Biology, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Data science, Workflow, 3111 Biomedicine, standards [Genomics], Human medicine, Software
Abstract

Correction to: Solving patients with rare diseases through programmatic reanalysis of genome-phenome data. Eur J Hum Genet. 2021 Sep;29(9):1466-1469. doi: 10.1038/s41431-021-00934-6. PMID: 34393220 Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257. Data were analysed using the RD‐Connect Genome‐Phenome Analysis Platform, which received funding from EU projects RD‐Connect, Solve-RD and EJP-RD (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática, INB) and ELIXIR Implementation Studies. We acknowledge support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya. We also acknowledge the support of the Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement and the Co-financing by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) with funds from the European Regional Development Fund (ERDF) corresponding to the 2014-2020 Smart Growth Operating Program. Sí

Published
2021
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46. Décryptage des mécanismes moléculaires menant au Spectre Oculo-Auriculo-Vertébral : de la recherche de gène aux modèles animaux

Author

Trimouille, Aurélien, U1211 Laboratoire Maladies Rares: Génétique et Métabolisme, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux, and Caroline Rooryck Thambo

Subjects
Next-Generation Sequencing, Spectre Oculo-Auriculo-Vertébral, Séquençage haut-Débit, Modèles animaux, Oculo-Auriculo-Vertebral Spectrum, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Animal models
Abstract

Goldenhar syndrom, or Oculo-Auriculo-Vertebral Sepctrum (OAVS [MIM: 164210]), is an embryonicdevelopmental defect involving the first and second branchial arches. Defects associated with this syndromeare malformations of ears, eyes, mandibles and vertebrae. OAVS is the second most frequent embryonicmalformative spectrum of head and neck. The phenotype is highly heterogeneous, and includes hemifacialmicrosomia, asymmetric auricular dysplasia, epibulbar dermoid and vertebral malformations.Non genetic causes have been reported for OAVS, with several toxic expositions (retinoic acid,mycophenolate mofetil, etc…). Furthermore, genetic causes of OAVS have been described in patientsharbouring structural variants (22q11.2, HMX1, OTX2, etc…), or single nucleotide variants, notably of MYT1gene.The aim of this work is to identify molecular bases of OAVS with exome or genome sequencing, and toconfirm the deleterious effect of variants with functional studies. Notably, we use proteomic analysis oncellular models and zebrafish models, allowing study of craniofacial development.This work identified 3 responsible genes of OAVS: ZYG11B, ZIC3 and EYA3.Trio-based exome sequencing in patient identified a de novo nonsense variant in ZYG11B. The deleteriouseffect of this mutation on protein function has been shown by mutant surexpression in Hela cells, andtransient knockdown by morpholinos in zebrafish model.Exome and genome sequencing in a family affected by X-linked mild OAVS phenotype found an expansionof polyalanines in ZIC3 gene. We also found in two different families affected with OAVS the same missensevariant of EYA3 gene. We confirmed the deleterious effect of this variant with functional studies on Helacells and zebrafish model, which harbour craniofacial defects.Furthermore, differential diagnosis have been found in 3 patients, with mutations in SOX5, EFTUD2, andEYA1 genes. Finally, two other candidate genes have been identified, and will be investigated by functionalstudies: SIX5 and SNRNP70.This work allowed us to better understand molecular causes involved in OAVS. However, its limits force usto find new tools to further investigate this spectrum. Integration of OMICs technologies, toxicologicalstudies on animal models, and innovative biostatistics tools applied to genomic analyses could be relevant; Le syndrome de Goldenhar, ou spectre Oculo-Auriculo-Vertébral (OAVS [MIM: 164210]), est une anomalie du développement embryonnaire associant des malformations des structures dérivées des premier et second arcs branchiaux, notamment l'oreille, l'œil, la mandibule et les vertèbres. Il s’agit du deuxième spectre malformatif embryonnaire le plus fréquent de la tête et du cou. Le phénotype clinique esthétérogène et caractérisé par une microsomie hémifaciale, des anomalies auriculaires asymétriques, des dermoïdes épibulbaires, et des malformations vertébrales.Différentes causes non génétiques ont été rapportées dans l’OAVS, dont de nombreuses expositions toxiques (acide rétinoïque, mycophénolate mofetil, etc…). Par ailleurs, une origine génétique de l’OAVS aété rapportée chez des patients porteurs de variants de structure (locus 22q11.2, HMX1, OTX2, etc…), ou devariants ponctuels, touchant notamment MYT1, seul gène rapporté dans plusieurs études.L’objectif de ce travail a été, via l’application du séquençage de l’exome et du génome, d’identifier la ou les causes moléculaires de la survenue de l’OAVS chez des patients issus d’une cohorte de plus de 350 individus,et de confirmer cette identification de gènes par des études fonctionnelles. Celles-ci ont notamment utilisées des analyses en protéomique, à partir de modèles cellulaire et zebrafish, à même de permettre une étude de la morphologie cranio-faciale.Ce travail nous a permis d’identifier 3 gènes responsables d’OAVS : ZYG11B, ZIC3 et EYA3.Le séquençage de l’exome en trio chez un patient nous a permis d’identifier un variant non-sens de novo dugène ZYG11B. L’effet délétère de cette mutation sur la fonction de la protéine a pu être montré par surexpression de la forme mutée sur modèle cellulaire Hela, et par inactivation transitoire de zyg11 parmorpholinos sur modèle zebrafish.Dans une famille où ségrège sur un mode récessif lié à l’X un phénotype OAVS modéré, la réalisation du séquençage d’exomes et d’un génome a pu montrer une association de ces atteintes avec la présence d’une expansion de polyalanines du gène ZIC3.Enfin, nous avons identifié chez deux familles différentes la présence d’un même variant faux-sens du gèneEYA3 ségrègeant avec des atteintes de l’OAVS. L’effet délétère de cette mutation a été confirmé par la réalisation d’études fonctionnelles sur modèle cellulaire et modèle zebrafish, qui présente des malformations cranio-faciales.Par ailleurs, 3 diagnostics différentiels ont pu être fait chez des patients initialement considérés comme atteints d’OAVS, et concernant les gènes SOX5, EFTUD2, et EYA1. Enfin, deux autres gènes candidats ont pu être identifiés, et feront l’objet d’études fonctionnelles : SIX5 et SNRNP70.Si ce travail nous a permis de mieux comprendre les causes moléculaires impliquées dans l’OAVS, ses limites nous imposent de trouver de nouveaux outils pour poursuivre ces investigations. Parmi ceux-ci,l’intégration de technologies OMICs, l’identification de cibles après exposition toxique sur modèle animal,et l’utilisation de méthodes statistiques innovantes appliquées aux analyses génomiques semblent les plus pertinents.

Published
2020

47. Deciphering the molecular pathways leading to Oculo-Auriculo-Vertebral Spectrum : from gene identification to animal models

Author

Trimouille, Aurélien, U1211 Laboratoire Maladies Rares: Génétique et Métabolisme, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux, Caroline Rooryck Thambo, Rooryck Thambo, Caroline, Dubus, Pierre, Verloes, Alain, Odent, Sylvie, Arveiler, Benoît, and STAR, ABES

Subjects
Next-Generation Sequencing, Spectre Oculo-Auriculo-Vertébral, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Séquençage haut-Débit, Modèles animaux, Oculo-Auriculo-Vertebral Spectrum, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Animal models
Abstract

Goldenhar syndrom, or Oculo-Auriculo-Vertebral Sepctrum (OAVS [MIM: 164210]), is an embryonicdevelopmental defect involving the first and second branchial arches. Defects associated with this syndromeare malformations of ears, eyes, mandibles and vertebrae. OAVS is the second most frequent embryonicmalformative spectrum of head and neck. The phenotype is highly heterogeneous, and includes hemifacialmicrosomia, asymmetric auricular dysplasia, epibulbar dermoid and vertebral malformations.Non genetic causes have been reported for OAVS, with several toxic expositions (retinoic acid,mycophenolate mofetil, etc…). Furthermore, genetic causes of OAVS have been described in patientsharbouring structural variants (22q11.2, HMX1, OTX2, etc…), or single nucleotide variants, notably of MYT1gene.The aim of this work is to identify molecular bases of OAVS with exome or genome sequencing, and toconfirm the deleterious effect of variants with functional studies. Notably, we use proteomic analysis oncellular models and zebrafish models, allowing study of craniofacial development.This work identified 3 responsible genes of OAVS: ZYG11B, ZIC3 and EYA3.Trio-based exome sequencing in patient identified a de novo nonsense variant in ZYG11B. The deleteriouseffect of this mutation on protein function has been shown by mutant surexpression in Hela cells, andtransient knockdown by morpholinos in zebrafish model.Exome and genome sequencing in a family affected by X-linked mild OAVS phenotype found an expansionof polyalanines in ZIC3 gene. We also found in two different families affected with OAVS the same missensevariant of EYA3 gene. We confirmed the deleterious effect of this variant with functional studies on Helacells and zebrafish model, which harbour craniofacial defects.Furthermore, differential diagnosis have been found in 3 patients, with mutations in SOX5, EFTUD2, andEYA1 genes. Finally, two other candidate genes have been identified, and will be investigated by functionalstudies: SIX5 and SNRNP70.This work allowed us to better understand molecular causes involved in OAVS. However, its limits force usto find new tools to further investigate this spectrum. Integration of OMICs technologies, toxicologicalstudies on animal models, and innovative biostatistics tools applied to genomic analyses could be relevant, Le syndrome de Goldenhar, ou spectre Oculo-Auriculo-Vertébral (OAVS [MIM: 164210]), est une anomalie du développement embryonnaire associant des malformations des structures dérivées des premier et second arcs branchiaux, notamment l'oreille, l'œil, la mandibule et les vertèbres. Il s’agit du deuxième spectre malformatif embryonnaire le plus fréquent de la tête et du cou. Le phénotype clinique esthétérogène et caractérisé par une microsomie hémifaciale, des anomalies auriculaires asymétriques, des dermoïdes épibulbaires, et des malformations vertébrales.Différentes causes non génétiques ont été rapportées dans l’OAVS, dont de nombreuses expositions toxiques (acide rétinoïque, mycophénolate mofetil, etc…). Par ailleurs, une origine génétique de l’OAVS aété rapportée chez des patients porteurs de variants de structure (locus 22q11.2, HMX1, OTX2, etc…), ou devariants ponctuels, touchant notamment MYT1, seul gène rapporté dans plusieurs études.L’objectif de ce travail a été, via l’application du séquençage de l’exome et du génome, d’identifier la ou les causes moléculaires de la survenue de l’OAVS chez des patients issus d’une cohorte de plus de 350 individus,et de confirmer cette identification de gènes par des études fonctionnelles. Celles-ci ont notamment utilisées des analyses en protéomique, à partir de modèles cellulaire et zebrafish, à même de permettre une étude de la morphologie cranio-faciale.Ce travail nous a permis d’identifier 3 gènes responsables d’OAVS : ZYG11B, ZIC3 et EYA3.Le séquençage de l’exome en trio chez un patient nous a permis d’identifier un variant non-sens de novo dugène ZYG11B. L’effet délétère de cette mutation sur la fonction de la protéine a pu être montré par surexpression de la forme mutée sur modèle cellulaire Hela, et par inactivation transitoire de zyg11 parmorpholinos sur modèle zebrafish.Dans une famille où ségrège sur un mode récessif lié à l’X un phénotype OAVS modéré, la réalisation du séquençage d’exomes et d’un génome a pu montrer une association de ces atteintes avec la présence d’une expansion de polyalanines du gène ZIC3.Enfin, nous avons identifié chez deux familles différentes la présence d’un même variant faux-sens du gèneEYA3 ségrègeant avec des atteintes de l’OAVS. L’effet délétère de cette mutation a été confirmé par la réalisation d’études fonctionnelles sur modèle cellulaire et modèle zebrafish, qui présente des malformations cranio-faciales.Par ailleurs, 3 diagnostics différentiels ont pu être fait chez des patients initialement considérés comme atteints d’OAVS, et concernant les gènes SOX5, EFTUD2, et EYA1. Enfin, deux autres gènes candidats ont pu être identifiés, et feront l’objet d’études fonctionnelles : SIX5 et SNRNP70.Si ce travail nous a permis de mieux comprendre les causes moléculaires impliquées dans l’OAVS, ses limites nous imposent de trouver de nouveaux outils pour poursuivre ces investigations. Parmi ceux-ci,l’intégration de technologies OMICs, l’identification de cibles après exposition toxique sur modèle animal,et l’utilisation de méthodes statistiques innovantes appliquées aux analyses génomiques semblent les plus pertinents.

Published
2020

48. Additional file 1 of Foetal onset of EIF2B related disorder in two siblings: cerebellar hypoplasia with absent Bergmann glia and severe hypomyelination

Author

Trimouille, Aurélien, Marguet, Florent, Sauvestre, Fanny, Lasseaux, Eulalie, Pelluard, Fanny, Marie-Laure Martin-Négrier, Plaisant, Claudio, Rooryck, Caroline, Lacombe, Didier, Arveiler, Benoît, Boespflug-Tanguy, Odile, Naudion, Sophie, and Laquerrière, Annie

Subjects
Data_FILES
Abstract

Additional file 1.

Published
2020
Full Text
View/download PDF

49. Additional file 2 of Foetal onset of EIF2B related disorder in two siblings: cerebellar hypoplasia with absent Bergmann glia and severe hypomyelination

Author

Trimouille, Aurélien, Marguet, Florent, Sauvestre, Fanny, Lasseaux, Eulalie, Pelluard, Fanny, Marie-Laure Martin-Négrier, Plaisant, Claudio, Rooryck, Caroline, Lacombe, Didier, Arveiler, Benoît, Boespflug-Tanguy, Odile, Naudion, Sophie, and Laquerrière, Annie

Subjects
Data_FILES
Abstract

Additional file 2.

Published
2020
Full Text
View/download PDF

50. Description of a family with X-linked oculo‐auriculo‐vertebral spectrum associated with polyalanine tract expansion in ZIC3

Author

Trimouille, Aurélien, Tingaud-Sequeira, Angèle, Lacombe, Didier, Hjortshøj, Tina Duelund, Kreiborg, Sven, Hove, Hanne Buciek, Rooryck, Caroline, Trimouille, Aurélien, Tingaud-Sequeira, Angèle, Lacombe, Didier, Hjortshøj, Tina Duelund, Kreiborg, Sven, Hove, Hanne Buciek, and Rooryck, Caroline

Abstract

Oculo-Auriculo-Vertebral Spectrum (OAVS) [MIM:164210], or Goldenhar syndrome, is a developmental disorder associating defects of structures derived from the first and second branchial arches. The genetic origin of OAVS is supported by the description of rare deleterious variants in a few causative genes, and several chromosomal copy-number variations. We describe here a large family with eight male members affected by a mild form of the spectrum, mostly auricular defects, harboring a hemizygous ZIC3 variant detected by familial exome sequencing: c.159_161dup p.(Ala55dup), resulting in an expansion of the normal 10 consecutive alanine residues to 11 alanines. Segregation analysis shows its presence in all the affected individuals, with a recessive X-linked transmission. Whole genome sequencing (WGS) performed in another affected male allowed to exclude linkage disequilibrium between this ZIC3 variant and another potential pathogenic variant in this family. Furthermore, by screening of a cohort of 274 OAVS patients, we found one male patient carrying an expansion of 10 to 12 alanines, a variant previously reported in patient presenting with VACTERL. Loss of function variants of ZIC3 are causing heterotaxy or cardiac malformations. These alanine expansion variants could have a different impact on the protein and thereby resulting in a different phenotype within the OAV spectrum/VACTERL.

Published
2020

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