Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

American journal of human genetics

Publication Date

12/1993

Volume

53

Pages

1180 - 1185

Addresses

Cardiology Division, Brigham and Women's Hospital, Boston, MA.

Keywords

Humans, Cardiomyopathy, Hypertrophic, Myosins, DNA Primers, Electrophoresis, Polyacrylamide Gel, Pedigree, Base Sequence, Haplotypes, Mutation, Polymorphism, Genetic, Molecular Sequence Data, Female, Male