Targeted next-generation sequencing of candidate genes reveals novel mutations in patients with dilated cardiomyopathy

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 lo...

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Bibliographic Details
Published in:International journal of molecular medicine 2015-12, Vol.36 (6), p.1479-1486
Main Authors: ZHAO, YUE, FENG, YUE, ZHANG, YUN-MEI, DING, XIAO-XUE, SONG, YU-ZHU, ZHANG, A-MEI, LIU, LI, ZHANG, HONG, DING, JIA-HUAN, XIA, XUE-SHAN
Format: Article
Language:English
Subjects:
candidate genes
Cardiomyopathy
Cardiomyopathy, Dilated
Care and treatment
Deoxyribonucleic acid
Development and progression
dilated cardiomyopathy
DNA
DNA sequencing
Gene mutations
Genes
Genetic aspects
Genetic testing
Genomes
Health aspects
Methods
Mitochondrial DNA
Mutation
next-generation sequencing
Nucleotide sequencing
Patients
Prognosis
Proteins
Software
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Summary: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.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2015.2361