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Independent origin of identical cardiac myosin heavy-chain mutations in hypertrophic cardiomyopathy

Item Type:Article
Title:Independent origin of identical cardiac myosin heavy-chain mutations in hypertrophic cardiomyopathy
Creators Name:Watkins, H., Thierfelder, L.H., Anan, R., Jarcho, J., Matsumori, A., McKenna, W., Seidman, J.G. and Seidman, C.E.
Abstract:The origins of the beta cardiac myosin heavy-chain (MHC) gene missense mutations that cause familial hypertrophic cardiomyopathy (FHC) in 14 families have been evaluated. Of eight different mutations, four were present in single families, while four occurred in two or more families. To investigate the origins of the four shared mutations, we defined the beta cardiac MHC haplotypes of each of the mutation-bearing chromosomes by determining the alleles present at three intragenic polymorphic loci. Two of the mutations (Arg453Cys and Val606Met) have arisen independently in each of three families, being found on different chromosomal backgrounds. A third mutation (Gly584Arg) is associated with identical haplotypes in two families with Portuguese ancestors, suggesting a founder effect. Haplotype analysis was uninformative for the fourth mutation (Arg403Gln). Thus, FHC-causing mutations have arisen independently in at least 12 of the 14 families studied, suggesting that the majority have arisen relatively recently as new mutations. This finding predicts the prevalence of disease-causing beta cardiac MHC mutations to be comparable in all population groups.
Keywords:Base Sequence, Hypertrophic Cardiomyopathy, DNA Primers, Polyacrylamide Gel Electrophoresis, Haplotypes, Molecular Sequence Data, Mutation, Myosins, Pedigree, Genetic Polymorphism
Source:American Journal of Human Genetics
Publisher:University of Chicago Press
Page Range:1180-1185
Date:December 1993
Official Publication:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682496/
PubMed:View item in PubMed

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