Identification and characterisation of a novel gene for cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a disease characterised by hypertrophy of the left ventricle of the heart. HCM has a prevalence of ~1 in 500 individuals and is the leading cause of sudden cardiac death among young individuals. Over 20 HCM genes have been identified but at least 20% of cases remain of unknown aetiology. An extended family presented to the Victorian Clinical Genetics Service with a syndromic form of HCM. Copy number analysis and linkage studies were performed using data from high density SNP-array analysis. A single linkage region was identified and no CNVs of interest were detected. Whole exome sequencing identified a homozygous truncating variant. To determine the potential contribution of the gene to HCM, we sequenced the gene in a cohort of HCM patients. We did not identify any predicted pathogenic variants. To investigate the function of the gene we have characterised the expression and splicing patterns in human and mouse tissues. Immunocytochemical studies demonstrated predominant localisation to the extracellular matrix. In conclusion:, we have identified a novel gene for HCM. Further characterisation of this protein will lead to increased understanding of the molecular basis of cardiomyopathy and result in improved clinical outcomes for affected individuals and families.