Whole exome sequencing identifies novel candidate mutations in a Chinese family with left ventricular noncompaction

Left ventricular noncompaction (LVNC) is an inherited cardiomyopathy involving numerous genes. To identify novel candidate causal mutations, a whole exome sequencing study was performed on a Chinese LVNC family. Exons of the most prevalent pathogenic genes of LVNC (myosin heavy chain 7 and actin, α‑cardiac muscle 1) were sequenced, although no mutations were identified. Following this, Burrows‑Wheeler Aligner, PICARD and Genome Analysis Toolkit (v.2.8) were used to analyze the exome sequencing data. Non‑silent single nucleotide variants (SNVs) that were identified in patients with LVNC, although not in the healthy individual, were investigated further using SNV prioritization via the integration of genomic data (SPRING) based on P‑values. Co‑expressed gene enrichment analysis was performed using Genotype Tissue Expression (GTEx) data in order to investigate the potential roles of the genes containing SNVs in the myocardium. In the Chinese LVNC family, seven novel SNVs were identified that were only present in patients with LVNC and annotated by SPRING with P<0.05. Among these SNVs, hemicentin 1 [c. thymine (T) 9776 cytosine (C)], tolloid like 2 [c. cytosine (C) 2615 thymine (T)], fms related tyrosine kinase 3 [c. guanine (G) 976 adenine (A)] and nucleotide binding protein like [c. guanine (G) 91 thymine (T)] were located in conserved regions and annotated as deleterious by PolyPhen2, LRT and MutationTaster database analyses. Based on GTEx data, it was revealed that NUBPL was co‑expressed with almost all previously established LVNC pathogenic genes. Furthermore, the results of the present study demonstrated that genes co‑expressed with NUBPL were additionally enriched in the Notch signaling pathway. In addition, the results revealed numerous novel mutations that may be causal SNVs for the development of LVNC in the family involved in the present study.