Whole-Exome Sequencing Identifies a Novel Mutation of Desmocollin 2 in a Chinese Family With Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare heart disorder characterized by myocyte loss and fibro-fatty tissue replacement. With the progress of ARVC, patient can present serious ventricular arrhythmias, heart failure and even sudden cardiac death. Previous study have...

Full description

Saved in:
Bibliographic Details
Published in:The American journal of cardiology 2017-05, Vol.119 (9), p.1485-1489
Main Authors: Liu, Ji-shi, M.D, Fan, Liang-liang, PH.D, Li, Jing-jing, B.S, Xiang, Rong, PH.D
Format: Article
Language:English
Subjects:
Adult
Aged
Arrhythmogenic Right Ventricular Dysplasia - genetics
Asian Continental Ancestry Group
Bioinformatics
Cardiac arrhythmia
Cardiomyopathy
Cardiovascular
Catenin
Damage
Desmocollin
Desmocollins - genetics
Desmosomes
Exome - genetics
Family medical history
Female
Gene sequencing
Genes
Genetic counseling
Genetic screening
Heart
Heart diseases
Humans
Localization
Male
Methionine
Middle Aged
Missense mutation
Mutation
Mutation, Missense
NMR
Nuclear magnetic resonance
Pathogenesis
Patients
Pedigree
Sequence Analysis, DNA
Ultrasonic imaging
Valine
Ventricle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare heart disorder characterized by myocyte loss and fibro-fatty tissue replacement. With the progress of ARVC, patient can present serious ventricular arrhythmias, heart failure and even sudden cardiac death. Previous study have revealed that the generation and development of ARVC are related to structural changes of desmosomes. To date, at least 5 genes associated with desmosomes have been identified in ARVC patients, including Desmoplakin , Plakophilin 2 , Desmoglein 2 , Desmocollin 2 , and Junction plakoglobin . In this study, we applied whole-exome sequencing to explore the potential causative gene in a Chinese family with suspicious ARVC. A novel missense mutation (c.1090G>A/p.V364M) of DSC2 was identified and co-segregated with the affected family members. This mutation leads to a substitution of valine by methionine and is predicted to be damaging by bioinformatics tools. In conclusion, our study not only expands the spectrum of DSC2 mutations and contributes to genetic counseling of families with ARVC, but also improves the awareness of pathogenesis in Chinese ARVC patients.
ISSN:0002-9149
1879-1913
DOI:10.1016/j.amjcard.2017.01.011