Academic Journal
Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
| العنوان: | Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls |
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| المؤلفون: | Walsh, Roddy, Lahrouchi, Najim, Tadros, Rafik, Kyndt, Florence, Glinge, Charlotte, Postema, Pieter, Amin, Ahmad, Nannenberg, Eline, Ware, James, Whiffin, Nicola, Mazzarotto, Francesco, Škorić-Milosavljević, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt, Bézieau, Stéphane, Bos, J Martijn, Breckpot, Jeroen, Campuzano, Oscar, Castelletti, Silvia, Celen, Candan, Clauss, Sebastian, Corveleyn, Anniek, Crotti, Lia, Dagradi, Federica, de Asmundis, Carlo, Denjoy, Isabelle, Dittmann, Sven, Ellinor, Patrick, Ortuño, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jørgen, Kimoto, Hiroki, Kotta, Maria-Christina, Krapels, Ingrid, Kurabayashi, Masahiko, Lazarte, Julieta, Leenhardt, Antoine, Loeys, Bart, Lundin, Catarina, Makiyama, Takeru, Mansourati, Jacques, Martins, Raphaël, Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frédéric, Sahin, Hatice, Sarquella-Brugada, Georgia, Sebastiano, Regina, Sharma, Sanjay, Sheppard, Mary, Shimamoto, Keiko, Shoemaker, M Benjamin, Stallmeyer, Birgit, Steinfurt, Johannes, Tanaka, Yuji, Tester, David, Usuda, Keisuke, van Der Zwaag, Paul, van Dooren, Sonia, van Laer, Lut, Winbo, Annika, Winkel, Bo, Yamagata, Kenichiro, Zumhagen, Sven, Volders, Paul, Lubitz, Steven, Antzelevitch, Charles, Platonov, Pyotr, Odening, Katja, Roden, Dan, Roberts, Jason, Skinner, Jonathan, Tfelt-Hansen, Jacob, van den Berg, Maarten, Olesen, Morten, Lambiase, Pier, Borggrefe, Martin, Hayashi, Kenshi, Rydberg, Annika, Nakajima, Tadashi, Yoshinaga, Masao, Saenen, Johan, Kääb, Stefan, Brugada, Pedro, Robyns, Tomas, Giachino, Daniela, Ackerman, Michael, Brugada, Ramon, Brugada, Josep, Gimeno, Juan, Hasdemir, Can, Guicheney, Pascale, Priori, Silvia, Schulze-Bahr, Eric, Makita, Naomasa, Schwartz, Peter, Shimizu, Wataru, Aiba, Takeshi, Schott, Jean-Jacques, Redon, Richard, Ohno, Seiko, Probst, Vincent, Behr, Elijah, Barc, Julien, Bezzina, Connie |
| المساهمون: | ITX - unité de recherche de l'institut du thorax (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition CHU Pitié Salpêtrière (IHU ICAN), CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
| المصدر: | ISSN: 1098-3600. |
| بيانات النشر: | CCSD Nature Publishing Group |
| سنة النشر: | 2020 |
| المجموعة: | Université de Nantes: HAL-UNIV-NANTES |
| مصطلحات موضوعية: | ACMG/AMP guidelines, Brugada, LQTS, variant interpretation, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10-18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10-13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/32893267; PUBMED: 32893267 |
| DOI: | 10.1038/s41436-020 |
| الاتاحة: | https://hal.sorbonne-universite.fr/hal-02946962 https://hal.sorbonne-universite.fr/hal-02946962v1/document https://hal.sorbonne-universite.fr/hal-02946962v1/file/s41436-020-00946-5.pdf https://doi.org/10.1038/s41436-020 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.49E0FFCF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41436-020 |
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