CCMB scientists discover rare gene mutations behind inherited heart disease

Scientists from the CSIR-Centre for Cellular and Molecular Biology (CCMB), in collaboration with researchers from Osmania University and AIG Hospitals, have identified two rare genetic mutations linked to Hypertrophic Cardio-Myopathy (HCM), a potentially life-threatening inherited heart disease that can lead to heart failure and sudden cardiac death.

Heart disease remains the leading cause of death worldwide and is a major health burden in India, particularly among people aged 35 to 64 years. The heart is a muscular organ that pumps blood throughout the body through a coordinated cycle of relaxation and contraction.

It consists of four chambers, with the upper chambers called the atria and the lower chambers known as the ventricles. The right side of the heart pumps oxygen-poor blood to the lungs, while the left side circulates oxygen-rich blood to the rest of the body. This continuous process ensures a steady supply of oxygen and nutrients to organs and tissues.

The heart’s pumping action is driven by specialised force-generating proteins within heart muscle cells. One such protein is beta-myosin heavy chain, encoded by the MYH7 gene, which plays a crucial role in generating the force required for heart muscle contraction.

In HCM patients, the heart muscle becomes abnormally thick, making it harder for the heart to relax and pump blood efficiently. The condition can cause breathlessness, chest pain, abnormal heart rhythms and, in severe cases, heart failure or sudden cardiac death.

CCMB scientists led by Deepa Selvi Rani and Kumarasamy Thangaraj, OU’s Pratibha Nallari and AIG Hospitals Dr. Calambur Narasimhan, analysed the MYH7 gene in 160 patients with HCM and 178 healthy individuals from Telangana. Of the 34 genetic variants identified, two rare mutations stood out as particularly significant. Both were located in critical regions of the myosin protein and are believed to impair normal heart muscle contraction.

One mutation was found in a 52-year-old woman with severe heart-muscle thickening and her 26-year-old son, who exhibited milder symptoms. The second mutation was identified in a 58-year-old man with obstructive HCM and a family history of sudden cardiac death. His 24-year-old daughter, who carried the same mutation, also showed mild thickening of the heart muscle.

Dr. Thangaraj said both variants were classified as “likely pathogenic” based on clinical, genetic and structural evidence. These variants were absent in healthy individuals and in major global population databases, suggesting that these variants are rare and may be enriched in Indian or South Asian populations.

The findings, published in the Journal of the American College of Cardiology: Asia, could pave the way for earlier diagnosis, targeted treatment and family-based screening. CCMB Director Vinay Nandicoori said that the study strengthens understanding of the genetic basis of inherited cardiovascular diseases and could support precision diagnosis and population screening in the future, according to an official release on Thursday.