Genetic mutations behind cardiomyopathy
doi:10.1038/nindia.2014.59 Published online 28 April 2014
Scientists have pinpointed rare mutations in the RAF1 gene that could be behind the heart condition 'dilated cardiomyopathy' (DCM). DCM, marked by left ventricle dilation and systolic dysfunction, affects around one in 250 people .
The RAF mutants, identified in three cohorts (South Indian, North Indian and Japanese), were expressed in zebrafish embryos. The researchers found that the embryos suffered heart failures with hyperactivation of the protein kinase AKT. The embryos were treated with rapamycin to restore health.
The cause of DCM remains unknown and there is no gene-specific therapy available till now.
The researchers resequenced 53 DCM cases and 50 matched controls from cohorts of distinct ancestry. They discovered RAF1 mutations in three of the cohorts from south India, north India and Japan. The prevalence of RAF1 mutations was approximately 9% in childhood-onset DCM cases in these three cohorts.
The researchers says that the findings could provide new mechanistic insights and potential therapeutic targets for RAF1-associated DCM. The study also opens up the possibility of expanding it to other RAF1-related human disorders.
- Dhandapany, P. S. et al. RAF1 mutations in childhood-onset dilated cardiomyopathy. Nat. Genet. (2014) doi: 10.1038/ng.2963