Striking Cardiac Phenotypic Variability in A Chinese Family With A MYH7 Splice Site Mutation

Abstract Background: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital heart defect (CHD), genetics defects have been found in patients with LVNC and their family members; and MYH7 is the most common genetic associated with LVNC. Methods: A trio (fetus and the parents) whole-exome sequencing (WES) was performed when the fetus was found with Ebstein's anomaly (EA), heart dilatation, perimembranous ventricular septal defects (VSD), mild seroperitoneum and single umbilical artery (SUA).Results: Whole-exome sequencing identified a maternal inherited heterozygous splice site mutation in MYH7 (NM_000257.3:c.732+1G>A). Subsequent Sanger sequencing confirmed that the mutation was heterozygous in the fetus, the old sister, the grandmother, and the mother. QPCR experiment using RNA from blood lymphocytes but were unable to amplify any product.Conclusion: This familial case underlines that the striking cardiac phenotypic of MYH7 mutation (the c.732+1G>A spice site variant) may be highly variable. The mechanistic studies which could uncover candidate genes modulating cardiac phenotype associated with LVNC/EA should be proceed.