ABSTRACT
Hypertrophic cardiomyopathy (HCM) is a heterogenous heart muscle disease predominantly caused by sarcomeric protein encoding genes. However, the cause for a significant number of elderly patients remains unclear. Here, we performed whole-exome sequencing in a South Indian family with an elderly HCM proband. We identified a heterozygous missense variant in the Nebulin-Related-Anchoring Protein encoding gene NRAP (NM_001261463, c.1259A>G, p.Y420C) in the proband. NRAP is a multi-domain scaffolding protein involved in cardiac muscle thin filament assembly, myofibril and actin cytoskeleton organization. The respective NRAP (p.Y420C) is predicted to be pathological by in-silico analysis and might be potentially influencing its functions. Targeted re-sequencing in an independent cohort resulted in identification of the same amino acid change in an unrelated eighty-six years old patient. The protein-protein interactions (PPI) network analysis revealed NRAP is strongly associated with other known elderly and late-onset HCM genes/proteins. In line with these data, both the study patients are late-onset in nature. Our study for the first time reveals the association of NRAP in the elderly and late-onset HCM patients and further expands the genotypic-phenotypic spectrum of HCM.
Footnotes
CONFLICT OF INTEREST: We declare no conflict of interest