title: Genetic heterogeneity for autosomal dominant familial hypertrophic cardiomyopathy in a Pakistani family.
abstract: OBJECTIVE
  To identify the gene causing inherited hypertrophic cardiomyopathy (HCM) in a Pakistani family.
  
  
  METHODS
  Cross-sectional, observational study.
  
  
  METHODS
  Department of Cardiology, Shifa International Hospital and Biomedical and Genetic Engineering Laboratories, Islamabad, from 2005 to 2007.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi.
authors: Aiysha
authors: A
authors: Abid
authors: Naveed
authors: N
authors: Akhtar
authors: Shagufta
authors: S
authors: Khaliq
authors: S Qasim
authors: SQ
authors: Mehdi
mesh_terms: D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D010154:Pakistan; D010375:Pedigree; D017422:Sequence Analysis, DNA; D019210:Troponin I / Q000235:genetics; D020107:Troponin T / Q000235:genetics
chemical_list: C545568:TNNT2 protein, human; D019210:Troponin I; D020107:Troponin T