CCMB scientists identify gene mutations responsible for hereditary heart disease

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

According to a report by The Hindu, heart disease is a leading cause of death worldwide and is a significant health burden in India, particularly among people aged 35 to 64. The heart is a muscular organ that pumps blood throughout the body. It consists of four chambers, with the upper sections called atria and the lower sections called ventricles. Deoxygenated blood is sent to the lungs via the right side of the heart, while oxygenated blood is delivered to the rest of the body via the left side.

The process of heart pumping is controlled by specific proteins located in the heart muscle cells. There is a protein called beta-myosin heavy chain, encoded by the MYH7 gene, which plays a crucial role in generating the force necessary for the contraction of heart muscles. In patients with HCM, the heart muscles become abnormally thick, making it difficult for the heart to pump blood. This condition leads to problems such as shortness of breath, chest pain, and irregularities in heartbeat.

CCMB scientists led by Deepa Selvi Rani and Kumarasamy Thangaraj, along with Pratibha Nallari of Osmania University and Dr. Kalambur Narasimha of AIG Hospital, analysed the MYH7 gene of 160 HCM patients and 178 healthy individuals from Telangana. During this investigation, 34 genetic variants were found, of which two rare mutations were found to be extremely significant. Both these mutations were observed in critical regions of the myosin protein, which obstruct the normal contraction of heart muscles.

During the research, one mutation was found in a 52-year-old woman whose heart muscles had become very thick, and this mutation was also found in her 26-year-old son, although his symptoms were mild. The second mutation was found in a 58-year-old man who had obstructive HCM and a family history of sudden cardiac death. His 24-year-old daughter also carried the same mutation and showed mild thickening of the heart muscles.

Dr. Thangaraj stated that based on clinical, genetic, and structural evidence, both these variants have been classified as "likely pathogenic". These variants have not been seen in healthy individuals or in global population databases, suggesting that these mutations are rare and may be more prevalent in the Indian or South Asian population.

This research has been published in the 'Journal of the American College of Cardiology: Asia', which could pave the way for early diagnosis, targeted treatment, and family screening. Vinay Nandikuri, Director of CCMB, stated in an official note that this study strengthens the understanding of the genetic basis of hereditary heart diseases and can be helpful in precise diagnosis and population screening in the future.