Whole-Exome Sequencing Identifies a Novel Mutation (p.L320R) of Alpha-Actinin 2 in a Chinese Family with Dilated Cardiomyopathy and Ventricular Tachycardia
- 11 January 2019
- journal article
- research article
- Published by S. Karger AG in Cytogenetic and Genome Research
- Vol. 157 (3), 148-152
- https://doi.org/10.1159/000496077
Abstract
Dilated cardiomyopathy (DCM) is a severe cardiovascular disease which can lead to heart failure and sudden cardiac death (SCD). The typical feature of DCM is left ventricular enlargement or dilatation. In some conditions, DCM and arrhythmia can occur concurrently, apparently promoting the prevalence of SCD. According to previous studies, mutations in more than 100 genes have been detected in DCM and/or arrhythmia patients. Here, we report a Chinese family with typical DCM, ventricular tachycardia, syncope, and SCD. Using whole-exome sequencing, a novel, likely pathogenic mutation (c.959T>G/p.L320R) of actinin alpha 2 (ACTN2) was identified in all affected family members. This novel mutation was also predicted to be disease-causing by MutationTaster, SIFT, and Polyphen-2. Our study not only expands the spectrum of ACTN2 mutations and contributes to the genetic diagnosis and counseling of the family, but also provides a new case with overlap phenotype that may be caused by the ACTN2 variant.Keywords
This publication has 25 references indexed in Scilit:
- Personalized genomic disease risk of volunteersProceedings of the National Academy of Sciences of the United States of America, 2013
- Dilated cardiomyopathy: the complexity of a diverse genetic architectureNature Reviews Cardiology, 2013
- Genetics of sudden cardiac death in children and young athletesCardiology in the Young, 2012
- α‐Actinin2 is required for the lateral alignment ofZdiscs and ventricular chamber enlargement during zebrafish cardiogenesisThe FASEB Journal, 2012
- A novel custom resequencing array for dilated cardiomyopathyGenetics in Medicine, 2010
- Mutations in Alpha-Actinin-2 Cause Hypertrophic Cardiomyopathy: A Genome-Wide AnalysisJournal of the American College of Cardiology, 2010
- Cell Membrane Expression of Cardiac Sodium Channel Nav1.5 Is Modulated by α-Actinin-2 InteractionBiochemistry, 2009
- Mutations in the muscle LIM protein and α-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosisMolecular Genetics and Metabolism, 2003
- Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy. A population-based study in Olmsted County, Minnesota, 1975-1984.Circulation, 1989