Exome Sequencing Identifies a Novel DES Mutation (R227C) in a Chinese Dilated Cardiomyopathy Family.
OBJECTIVE
Dilated cardiomyopathy (DCM) is a common disease in the clinic, and it is the leading cause of heart failure and sudden cardiac death. Previous studies have proven that genetic factors play a crucial role in the occurrence of DCM; more than 50 disease genes including desmin (DES) have been identified to be associated with DCM. At present, most DES mutations are reported in desmin-related myofibrilla myopathy patients, but variants leading to isolated DCM are rarely reported.


METHODS
We applied whole-exome sequencing and cardiomyopathy-related gene filtering strategies to discover the genetic factors in a Chinese DCM family.


RESULTS
A novel mutation (c.679 C>T /p.R227C) in exon 3 of DES was identified and cosegregated with the affected members of a Chinese family with isolated DCM phenotypes (left ventricle and left atrial diameters).


CONCLUSIONS
This mutation leads to a substitution of arginine by cysteine and it is predicted to be deleterious by bioinformatics programs. Our study not only contributes to the genetic diagnosis and counseling of families with DCM, but it also further proves that DES mutations may lead to isolated DCM and provides a new case for the study of the relationship between DES mutations and DCM.
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China.
Rong
R
Yu
Lv
L
Liu
Chan
C
Chen
Jin-Mei
JM
Shen
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000235:genetics*; D002681:China; D003893:Desmin / Q000235:genetics*; D004452:Echocardiography; D004562:Electrocardiography; D059472:Exome / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA
D003893:Desmin
DES; Dilated cardiomyopathy; Mutation; Whole-exome sequencing