Identification of gene mutation associated with familial dilated cardiomyopathy by whole-exome sequencing / 复旦学报（医学版）

ABSTRACT

Objective To identify the disease-causing gene in a Chinese pedigree with familial dilated cardiomyopathy (DCM) by whole-exome sequencing.Methods After collecting the clinical data and extracting the whole blood genomic DNA of the 5 family members form a Chinese DCM pedigree,whole-exome sequencing was performed to search the causative genes.Familial co-segregation analysis among the pedigree was subsequently confirmed by traditional Sanger sequencing.Results We performed whole exome sequencing (WES) on representative affected individuals and unaffected familial members from this pedigree.After comparison with variants identified in affected individuals and unaffected individuals,along with previously reported genetic mutations associated with DCM,we found that a heterozygous variant c.961 C＞T (p.Arg321Ter) in exon 6 of the LMNA gene in affected individuals matched the criteria to be the potential disease-causing gene,which was confirmed by Sanger sequencing.This stop-gain mutation leads to only a small part of LMNA-coding protein expressed,therefore we concluded that LMNA c.961 C＞T should be the causative mutation for this familial DCM case.Conclusions The nonsense mutation c.961 C＞ T in gene LMNA identified by whole-exome sequencing might be the pathogenic mutation in this DCM pedigree.