Beta myosin heavy chain gene mutations in hypertrophic, dilated and restrictive cardiomyopathy patients

Objectives: The aim of the study was to screen patients with different cardiomyopathy phenotypes for mutations in the human cardiac beta myosin heavy chain gene.

Background: Cardiomyopathies are a diverse and important group of heart muscle diseases often leading to cardiovascular morbidity and mortality. Sarcomeric gene mutations have been known to be associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and restrictive cardiomyopathy (RCM).

Methods and Results: We screened 136 consecutive patients [64 probands diagnosed with hypertrophic cardiomyopathy (HCM), 65 with dilated cardiomyopathy (DCM) and 7 with restrictive cardiomyopathy (RCM)] for mutations in the MYH7 gene. Four mutations were identified. Three mutations (p.Met515Thr, p.Tyr266Cys and p.Arg787His) were identified in HCM patients and one (p.Gly377Ser) in a DCM patient. The patient with p.Met515Thr had septal thickness of 19mm. She died at the age of 20 years. The patient with p.Tyr266Cys had severe left ventricular hypertrophy with a septal thickness of 32 mm and involvement of right ventricle. The patient with p.Arg787His mutation had apical hypertrophy. The patient with p.Gly377Ser mutation had DCM and a family history of sudden cardiac death. The age of onset of symptoms in the proband was 35 years. Three other family members aged 38, 18 and 14 years having the same mutation were identified but were found to be normal and were given genetic counseling. The mutation is associated with a late onset of the disease and a variable penetrance.

Conclusion: The genetic and phenotypic heterogeneity of HCM and DCM exists in the Indian population.