Rare gene mutations in heart disease involving kids found

A multinational team of scientists, including those from the Center for Cellular and Molecular Biology (CCMB), had found out  rare gene mutations in children affected with heart disease (commonly called dilated cardiomyopathy (DCM)), the observations of which were published recently in the scientific journal Nature Genetics.

The study, which sequenced a total of 513 patients (mostly children) and 1,150 ethnically matched DNAs of distinct ancestry from northern and southern India, Japan and Italy, discovered mutations (variations in DNA sequence) in a gene known as RAF1 among the Indian and Japanese descendants. It found out the prevalence of RAF1 mutations in 9 per cent of childhood-onset DCM cases.

The observation gathers key importance as 30-million Indians are suffering from heart disease every year. The finding could translate into discovery of new drugs that are more effective and economical, it said.

DCM is a condition in which the heart’s ability to pump blood is decreased as the heart’s pumping chamber becomes large and weak.

“This is the first predominant gene found for childhood DCM and we have also identified rapamycin as possible therapeutic option for such conditions,” said Dr PS Dhandapany, junior faculty at the Icahn School of Medicine at Mount Sinai, New York. He is also the lead author of this study.

In the team’s pursuit to obtain therapeutic cure, “experiments on zebrafish using Rapamycin drug has yielded positive results in regulating the RAF1 mutations and achieving normal heart state,” said Dr K Thangaraj, senior principal scientist, CCMB, Hyderabad. The team would later go for animal trials in rat and mouse, he added.

He said DCM was prevalent in the age group of 5-15 years and many of them die before turning into adults. The CCMB started research on cardiomyopathy in 2005 and published key findings in the subsequent years.

The study has been a concerted effort of CCMB; Department of Genetics and Genomic Sciences, Icahn School of Medicine, New York; Post Graduate Institute of Medical Education and Research, Chandigarh; Department of Advanced Zoology and Biotechnology, Loyola College, Chennai; Department of Pediatric Surgery, Tokyo Women's Medical University in Tokyo, and Monaldi Hospital, Second University of Naples, Italy.