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. Incardiomyopathies, phenotypic overlapping among the inherited cardiovascular diseases (CVDs) limits theability to establish a diagnosis based solely on clinical features. Here, we developed a next generationsequencing (NGS) assay to analyze a panel of 142 known cardiomyopathy genes in 9 Vietnamese patientsfrom 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 studiedVietnamese unrelated patients. Of 65 variants identified, 28 variants were homozygous and the other 37 oneswere heterozygous. Among the 65 variants, TTN gene variants accounted the most for 13 mutations, which areknown to be benign. Other groups of 9 and 8 mutations belong to SYNE1 and MYPN genes, respectively. Tenout of 65 mutations distributed equally to NDUFV2 and SCN5A gene variants. We detected 6 and 4 variantsfor SYNE2 and COX15 genes, respectively. Each gene of DMD, KCNE1, NEBL and RBM20 has 2 variants. Asingle 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. Thesegenetic results support the “pan-cardiomyopathy panel” approach, by which the molecular diagnosis ofcardiomyopathies, early identification of arrhythmia development and better clinical management ofcardiomyopathic patients are applied.