학술논문
Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy.
Document Type
article
Author
Irene Mademont-Soler; Jesus Mates; Raquel Yotti; Maria Angeles Espinosa; Alexandra Pérez-Serra; Ana Isabel Fernandez-Avila; Monica Coll; Irene Méndez; Anna Iglesias; Bernat Del Olmo; Helena Riuró; Sofía Cuenca; Catarina Allegue; Oscar Campuzano; Ferran Picó; Carles Ferrer-Costa; Patricia Álvarez; Sergio Castillo; Pablo Garcia-Pavia; Esther Gonzalez-Lopez; Laura Padron-Barthe; Aranzazu Díaz de Bustamante; María Teresa Darnaude; José Ignacio González-Hevia; Josep Brugada; Francisco Fernandez-Aviles; Ramon Brugada
Source
PLoS ONE, Vol 12, Iss 8, p e0181465 (2017)
Subject
Language
English
ISSN
1932-6203
Abstract
Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation.Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease.The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p