Role of modifying genes on the severity of rare mutation of MYH7 gene in hypertrophic obstructive cardiomyopathy

Abstract

Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder due to mutations in sacromeric genes with variable penetrance. Hypertrophic Obstructive Cardiomyopathy (HOCM) is a major complication of Hypertrophic Cardiomyopathy. Unexplained hypertrophy in the Left Ventricle (LV) or Intraventricular Septum (IVS) had been the diagnostic criterion for HCM which is more often confirmed by the echocardiography. The frequency of HCM in general population is 1:500 and about 60-70% genetic predisposition is known. It has been observed that mutations in the Cardiac myosin binding proteinC (MYBPC3) gene causes late onset of disease with mild symptoms while mutations in the Beta Myosin Heavy chain (MYH7) gene leads to early onset with severe symptoms. Apart from Epigenetic and Environmental factors, modifier genes further complicate the situation leading to altered clinical outcome even among the same family members having identical mutation.