title: Targeted next-generation sequencing of candidate genes reveals novel mutations in patients with dilated cardiomyopathy.
abstract: Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure, and it is characterized by genetic and clinical heterogeneity, even for some patients with a very poor clinical prognosis; in the majority of cases, DCM necessitates a heart transplant. Genetic mutations have long been considered to be associated with this disease. At present, mutations in over 50 genes related to DCM have been documented. This study was carried out to elucidate the characteristics of gene mutations in patients with DCM. The candidate genes that may cause DCM include MYBPC3, MYH6, MYH7, LMNA, TNNT2, TNNI3, MYPN, MYL3, TPM1, SCN5A, DES, ACTC1 and RBM20. Using next-generation sequencing (NGS) and subsequent mutation confirmation with traditional capillary Sanger sequencing analysis, possible causative non-synonymous mutations were identified in ~57% (12/21) of patients with DCM. As a result, 7 novel mutations (MYPN, p.E630K; TNNT2, p.G180A; MYH6, p.R1047C; TNNC1, p.D3V; DES, p.R386H; MYBPC3, p.C1124F; and MYL3, p.D126G), 3 variants of uncertain significance (RBM20, p.R1182H; MYH6, p.T1253M; and VCL, p.M209L), and 2 known mutations (MYH7, p.A26V and MYBPC3, p.R160W) were revealed to be associated with DCM. The mutations were most frequently found in the sarcomere (MYH6, MYBPC3, MYH7, TNNC1, TNNT2 and MYL3) and cytoskeletal (MYPN, DES and VCL) genes. As genetic testing is a useful tool in the clinical management of disease, testing for pathogenic mutations is beneficial to the treatment of patients with DCM and may assist in predicting disease risk for their family members before the onset of symptoms.
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Faculty of Life Science and Technology, Research Center for Molecular Medicine in Yunnan Province, Kunming University of Science and Technology, Kunming 650500, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Cardiology, The First Hospital of Yunnan Province, Kunming 650034, P.R. China.
authors.forename: Yun-Mei
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Hospital of Yunnan Province, Kunming 650034, P.R. China.
authors.forename: Xiao-Xue
authors.initials: XX
authors.lastname: Ding
authors.affiliation: Faculty of Life Science and Technology, Research Center for Molecular Medicine in Yunnan Province, Kunming University of Science and Technology, Kunming 650500, P.R. China.
authors.forename: Yu-Zhu
authors.initials: YZ
authors.lastname: Song
authors.affiliation: Faculty of Life Science and Technology, Research Center for Molecular Medicine in Yunnan Province, Kunming University of Science and Technology, Kunming 650500, P.R. China.
authors.forename: A-Mei
authors.initials: AM
authors.lastname: Zhang
authors.affiliation: Faculty of Life Science and Technology, Research Center for Molecular Medicine in Yunnan Province, Kunming University of Science and Technology, Kunming 650500, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Hospital of Yunnan Province, Kunming 650034, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, P.R. China.
authors.forename: Jia-Huan
authors.initials: JH
authors.lastname: Ding
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, P.R. China.
authors.forename: Xue-Shan
authors.initials: XS
authors.lastname: Xia
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity