Yang J, Zhu M, Wang Y, Hou X, Wu H, Wang D, Shen H, Hu Z, Zou J
BACKGROUND: Left ventricular noncompaction (LVNC) is a genetic cardiomyopathy results from the failure of myocardial development during embryogenesis. Previous reports show that defects in TAZ, SCN5A, TPM1, YWHAE, MYH7, ACTC1 and TNNT2 are associated with LVNC. Sequencing of individuals using family-based design is a powerful approach for hereditary disease. In this study, we used whole-exome sequencing to screen potentially novel causal mutations in a Chinese Han family with LVNC. METHODS: DNA from 3 individuals belonging to the same family was extracted and sequenced based on standard whole-exome sequencing protocol. The exome sequence data was analyzed using BWA, PICARD and Genome Analysis Toolkit (GATK v2.8). Non-silent single nucleotide variants (SNVs) were further selected if they exist in both LVNC patients and not in the health control. A web-based software Snv Prioritization via the INtegration of Genomic data (SPRING), was used to prioritize the causal SNV by calculating a q-value which indicates the statistical significance that a variant is causative for a query disease. RESULTS: From the LVNC family in which the mother and son were affected, a novel single nucleotide variant c.C1492G in exon 15 of MYH7 was identified probably to be the causal SNV of the family with P-value of 3.45E-05 and q-value of 4.65E-03 by SPRING. The SNV was predicted as deleterious in SIFT, PolyPhe2 and MutatioTaster database. Another 12 SNVs were also identified with P-value less than 0.05 by SPRING. CONCLUSIONS: A novel genetic variant in the coding regions of MYH7 gene was identified in a Chinese LVNC-family. The results support the previous evidence that MYH7 is a pathogenic gene for LVNC.