التفاصيل البيبلوغرافية
| العنوان: |
Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls |
| المؤلفون: |
Walsh, Roddy, Lahrouchi, Najim, Tadros, Rafik, Kyndt, Florence, Glinge, C ., Postema, P.G., Amin, Ahmad S., Nannenberg, E.A., Ware, J.S., Whiffin, N., Mazzarotto, F., Korić-Milosavljević, D., Krijger, C., Arbelo, Elena, Babuty, D., Barajas-Martinez, H., Beckmann, B.M., Bézieau, S., Bos, J.M., Breckpot, J., Campuzano Larrea, Oscar, Castelletti, S., Celen, C., Clauss, S., Corveleyn, A., Crotti, Lia, Dagradi, F., de Asmundis, C., Denjoy, Isabelle, Dittmann, S., Ellinor, P.T., Ortuño, C.G., Giustetto, Carla, Gourraud, Jean Baptiste, Hazeki, D., Horie, M., Ishikawa, T., Itoh, H. |
| المصدر: |
Genetics in Medicine, 2020, vol. 23, núm. 1, p. 47-58 ; Articles publicats (D-CM) ; Walsh, Roddy Lahrouchi, Najim Tadros, Rafik Kyndt, Florence Glinge C Postema PG Amin AS Nannenberg EA Ware JS Whiffin N Mazzarotto F korić-Milosavljević D Krijger C Arbelo E Babuty D Barajas-Martinez H Beckmann BM Bézieau S Bos JM Breckpot J Campuzano Larrea, Oscar Castelletti S Celen C Clauss S Corveleyn A Crotti L Dagradi F de Asmundis C Denjoy I Dittmann S Ellinor PT Ortuño CG Giustetto C Gourraud JB Hazeki D Horie M Ishikawa T Itoh H 2020 Enhancing rare variant interpretation in .... |
| بيانات النشر: |
Nature Publishing Group |
| سنة النشر: |
2020 |
| المجموعة: |
Universitat de Girona: DUGiDocs (UdG Digital Repository) |
| الوصف: |
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 |
| وصف الملف: |
12 p.; application/pdf |
| اللغة: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/issn/1098-3600; info:eu-repo/semantics/altIdentifier/eissn/1530-0366; http://hdl.handle.net/10256/24191 |
| الاتاحة: |
http://hdl.handle.net/10256/24191 |
| Rights: |
Reconeixement-NoComercial-SenseObraDerivada 4.0 Internacional ; http://creativecommons.org/licenses/by-nc-nd/4.0 ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.3B2BC779 |
| قاعدة البيانات: |
BASE |