Journal - Journal of the College of Physicians and Surgeons--Pakistan : JCPSP (Pakistan )

Abstract :

To identify the gene causing inherited hypertrophic cardiomyopathy (HCM) in a Pakistani family.Cross-sectional, observational study.Department of Cardiology, Shifa International Hospital and Biomedical and Genetic Engineering Laboratories, Islamabad, from 2005 to 2007.A large family of 17 individuals was included in this study. In the family 6 members were suffering from hypertrophic cardiomyopathy. Linkage analysis was carried out to map the disease-causing gene. Genomic DNA from each individual of the whole family was genotyped for microsatellite markers for all the known HCM loci followed by a whole genome search. Automated DNA sequencing was done for mutation identification in the candidate genes.Linkage analysis of 17 family members showed a maximum two point Lod score of 3.97 with marker D1S1660 at chromosome 1q 32.2. A disease region of 4.16cM was defined by proximal and distal cross-overs with markers GATA135F02 and D1S3715 respectively. This region contained the candidate genes TNNT2 (cardiac troponin T) and TNNI1 (troponin I 1). Direct sequencing of these genes for the whole family containing 17 members showed no diseaseassociated mutation in either of these genes.Through linkage analysis, a disease locus for HCM family was mapped within a region of 4.16cM at chromosome 1q31.3-q32.1. So far no disease-associated mutation has been found in the candidate genes.