Whole exome sequencing identified a novel myopalladin gene mutation in a cardiomyopathy patient

Abstract

Cardiomyopathies (CMs) are a heterogenous group of disorders that affects the heart muscle. In
cardiomyopathies, phenotypic overlapping among the inherited cardiovascular diseases (CVDs) limits the
ability to establish a diagnosis based solely on clinical features. Here, we developed a next generation
sequencing (NGS) assay to analyze a panel of 142 known cardiomyopathy genes in 9 Vietnamese patients
from Children Hospital 2, Hochiminh City and Medical University Hospital, Hochiminh City, Vietnam.
Whole exome sequencing (WES) - a technique which determines the variations of all coding regions (exons)
of the known genes - validated a total of 65 rare variants in 18 cardiomyopathy genes among the studied
Vietnamese unrelated patients. Of 65 variants identified, 28 variants were homozygous and the other 37 ones
were heterozygous. Among the 65 variants, TTN gene variants accounted the most for 13 mutations, which are
known to be benign. Other groups of 9 and 8 mutations belong to SYNE1 and MYPN genes, respectively. Ten
out of 65 mutations distributed equally to NDUFV2 and SCN5A gene variants. We detected 6 and 4 variants
for SYNE2 and COX15 genes, respectively. Each gene of DMD, KCNE1, NEBL and RBM20 has 2 variants. A
single variant was detected for AKAP9, CAV3, DSC2, DSG2, DSP, MYBPC3 and MYH6 genes. Especially,
among them, we found a novel heterozygous nonsynonymous mutation c.1527C>G on the MYPN gene. These
genetic results support the “pan-cardiomyopathy panel” approach, by which the molecular diagnosis of
cardiomyopathies, early identification of arrhythmia development and better clinical management of
cardiomyopathic patients are applied.