Human Molecular Genetics, Vol 4, 1721-1727, Copyright © 1995 by Oxford University Press
H Watkins, JG Seidman and CE Seidman
Familial hypertrophic cardiomyopathy is an autosomal dominant disorder
manifesting as cardiac hypertrophy in the absence of increased cardiac work
load, which has been studied as a model of myocardial hypertrophy in
humans. Hypertrophic cardiomyopathy is genetically heterogeneous with three
known disease-genes and two further mapped loci. The disease- genes encode
contractile proteins of the thick and thin filaments of the sarcomere: the
beta cardiac myosin heavy chain gene on chromosome 14q11, the alpha
tropomyosin gene on chromosome 15q2 and the cardiac troponin T gene on
chromosome 1q3. Other disease loci have been mapped to chromosome 11p13-q13
and 7q3. In each known disease-gene a number of different mutations have
been identified; these are missense mutations, or mutations leading to
modest alterations of peptide structure, but not null alleles. Specific
mutations are associated with different disease severity and may provide
diagnostic and prognostic information not available from clinical
assessment. Genetic and functional data suggest that mutations which cause
hypertrophic cardiomyopathy act as dominant negative alleles that impair
cross-bridge cycling and contractile function and interfere with sarcomere
assembly.
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Familial hypertrophic cardiomyopathy: a genetic model of cardiac hypertrophy
Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA, USA.
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