| Title: |
A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing |
| Authors: |
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; 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, E L M; 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; 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; 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; 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 |
| Contributors: |
Université Bourgogne Franche-Comté COMUE (UBFC); Lipides - Nutrition - Cancer Dijon - U1231 (LNC); Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon; Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro); Barcelona Institute of Science and Technology (BIST); Radboud University Nijmegen; The University of Edinburgh; Università degli Studi di Siena = University of Siena (UNISI); University of Manchester Manchester; Génétique des anomalies du développement (CTM UMR 1231) (GAD); Center for Translational and Molecular medicine Dijon - UMR1231 (CTM); École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon; Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-École Pratique des Hautes Études (EPHE); FHU TRANSLAD (CHU de Dijon); Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon); IRCCS Ospedale Pediatrico Bambino Gesù = Bambino Gesù Children’s Hospital; Manchester Centre for Genomic Medicine Manchester, UK (MCGM); St Mary's Hospital Manchester-Manchester Academic Health Science Centre (MAHSC); University of Manchester Manchester -University of Manchester Manchester -Manchester University NHS Foundation Trust (MFT)-Faculty of Biology, Medicine and Health Manchester, UK; Université de Bourgogne (UB); Equipe GAD (LNC - U1231); Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon; Eberhard Karls Universität Tübingen = University of Tübingen; Radboud University Medical Center Nijmegen (RadboudUMC); Universitätsklinikum Tübingen = University Hospital of Tuebingen; Univerzita Karlova Praha, Česká republika = Charles University Prague, Czech Republic = Université Charles Prague, Republique tchèque (UK); University Hospital Motol Prague; Universiteit van Amsterdam = University of Amsterdam (UvA); 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); Centre de recherche en Myologie – U974 SU-INSERM; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); Hospices Civils de Lyon (HCL); Service de Génétique HCL, Lyon (Centre de Référence des Anomalies du Développement); Génétique des anomalies du développement : GAD (CTM UMR 1231) (GAD); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon; Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université Bourgogne Europe (UBE)-École Pratique des Hautes Études (EPHE); Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université Bourgogne Europe (UBE); The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 779257. Data were analyzed using the RD-Connect Genome-Phenome Analysis Platform, which received funding from the EU projects RD-Connect, Solve-RD, and European Joint Programme on Rare Diseases (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), and ELIXIR Implementation Studies. The collaborations in this study were facilitated by the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies, one of the 24 European Reference Networks approved by the European Reference Network Board of Member States, cofunded by the European Commission. This project was supported by the Czech Ministry of Health (number 00064203) and by the Czech Ministry of Education, Youth and Sports (number - LM2018132) to M.M.; European Project: 779257,H2020-SC1-2016-2017,H2020-SC1-2017-Single-Stage-RTD,Solve-RD(2018); European Project: 825575,H2020-SC1-BHC-2018-2020,H2020-SC1-2018-Single-Stage-RTD,EJP RD(2019); European Project: 305444,FP7-HEALTH-2012-INNOVATION-1,FP7-HEALTH-2012-INNOVATION-1,RD-CONNECT(2012) |
| Source: |
ISSN: 1098-3600. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2023 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
ClinVar; Developmental disorder; Exome reanalysis; Rare diseases; [SDV.GEN]Life Sciences [q-bio]/Genetics |
| Description: |
International audience ; 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 singlenucleotide 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36681873; info:eu-repo/grantAgreement//779257/EU/Solving the unsolved Rare Diseases/Solve-RD; info:eu-repo/grantAgreement//825575/EU/European Joint Programme on Rare Diseases/EJP RD; info:eu-repo/grantAgreement//305444/EU/RD-CONNECT: An integrated platform connecting registries, biobanks and clinical bioinformatics for rare disease research/RD-CONNECT; PUBMED: 36681873 |
| DOI: |
10.1016/j.gim.2023.100018 |
| Availability: |
https://hal.science/hal-05290572; https://hal.science/hal-05290572v1/document; https://hal.science/hal-05290572v1/file/Denomme-Pichon%20et%20al.%202023.pdf; https://doi.org/10.1016/j.gim.2023.100018 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.E6DF3420 |
| Database: |
BASE |