Identification of a novel hypertrophic cardiomyopathy-associated mutation using targeted next-generation sequencing

Zhao,Yue; Feng,Yue; Ding,Xiaoxue; Dong,Shuwei; Zhang,Hong; Ding,Jiahuan; Xia,Xueshan

doi:10.3892/ijmm.2017.2986

Identification of a novel hypertrophic cardiomyopathy-associated mutation using targeted next-generation sequencing

Authors:
- Yue Zhao
- Yue Feng
- Xiaoxue Ding
- Shuwei Dong
- Hong Zhang
- Jiahuan Ding
- Xueshan Xia
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Affiliations: Faculty of Life Science and Technology, Research Center for Molecular Medicine in Yunnan Province, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China, Department of Cardiology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650034, P.R. China
Published online on: May 11, 2017 https://doi.org/10.3892/ijmm.2017.2986
Pages: 121-129
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypertrophic cardiomyopathy (HCM), one of the most common forms of myocardial diseases, is the major cause of sudden cardiac death in young adults and competitive athletes. Analyses of gene mutations associated with HCM are valuable for its molecular diagnosis, genetic counseling, and management of familial HCM. To dissect the relationship between the clinical presentation and gene mutations of HCM, the genetic characterizations of 19 HCM-related genes in 18 patients (8 cases from 6 pedigrees with familial HCM and 10 cases without familial HCM) were detected using next-generation sequencing (NGS). As a result, 12 disease-related mutations were identified in the 18 subjects, including 6 single mutations and 3 double mutations [MYBPC3 (p.Gln998Glu) plus TNNI3 (p.Arg145Gly), PRKAG2 (p.Gly100Ser) plus MYBPC3 (p.Lys1209Serfs*28) and TNNI3 (p.Glu124Gln) plus GLA (p.Trp47*)]. The 3 heterozygous double mutations were discovered for the first time in the malignant familial HCM patients. Of the 6 single mutations, a novel mutation was found in tafazzin (TAZ, p.Ile208Val), and a mutation in β-myosin heavy chain gene (MYH7, p.Arg54Gln), which was reported as rare in the general population, was firstly found in one HCM patient. Identification of novel and rare mutations in HCM patients have added new data to the spectrum of gene mutations associated with this disease. These findings provide an essential basis for the molecular diagnosis and better management of family members at risk of familial HCM.

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