Scientists have traced the early onset and severity of cardiomyopathy disease in a South Indian family to novel genetic mutations.
Cardiomyopathy is the disease of the heart muscle affecting its ability to contract and expand and could eventually lead to heart failure.
The main types include dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy.
In a paper published in a recent issue of DNA and Cell Biology by Deepa Selva Rani et al from the Centre for Cellular and Molecular Biology (CCMB), it was mentioned that mutations to sarcomeric genes are the leading cause for cardiomyopathies.
However, not many studies have been carried out on Indian cardiomyopathy patients.
Sarcomeric genes code proteins that are essential for contraction and expansion of heart muscle.
In the study, one of the sarcomeric genes, alpha-tropomyosin (TPM1) was screened for variants in 101 hypertrophic cardiomyopathy( HCM) patients and 147 dilated cardiomyopathy(DCM) patients against 207 ethnically matched healthy controls from South India. While 13 variants were detected in TPM1, another mutation-S215L (which was reported in an earlier study by the same group) was found in two unrelated individuals suffering from HCM.
However, the onset of the disease was early and the severity was greater in a younger 44-year-old individual compared to the other patient, who was 65 years old. The mutation was completely absent in DCM patients and controls.
Following this, the two individuals and their family members were screened to find if there were variations in seven more sarcomeric genes. Two novel mutations in MYH7 gene were identified exclusively in the 44-year-old patient and his family members.
The paper stated that the thick filament mutations, D896N and 1524K in the beta-myosin heavy chain were novel.
According to Dr.Deepa, the number of mutations was directly proportional to the severity of the disease.
She said the family also had two cases of sudden cardiac death. She said that sarcomeric genes were involved in maintaining the heart muscle structure and so far 11 sarcomeric genes were found to be responsible for cardiomyopathies.
Dr.K. Thangaraj, another author of the paper, said that this was the first study in India to find TPM1 gene mutation vis-à-vis cardio -myopathies.
He said it was very rare to find two pathogenic mutations in a single individual. Since marriage practices in South India were known for consanguineous nature, this finding was not very surprising.
The scientists also carried out further bioinformatics, biochemical and biophysical studies in collaboration with John A.Mercer from the National Centre for Biological Sciences, TIFR, Bengaluru and a few other institutions. The study, which was published in the March, 2015 issue of the Journal of Biological Chemistry , supported pathogenicity of the mutations.
Dr. Thangaraj said the finding would help in early diagnosis and planning treatment strategies for the disease.
