alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy

Citation
J. Mogensen et al., alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy, J CLIN INV, 103(10), 1999, pp. R39-R43
Citations number
28
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF CLINICAL INVESTIGATION
ISSN journal
00219738 → ACNP
Volume
103
Issue
10
Year of publication
1999
Pages
R39 - R43
Database
ISI
SICI code
0021-9738(199905)103:10<R39:AAIAND>2.0.ZU;2-E
Abstract
We identified the a-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, show ing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala29 5Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible f or 2 different cardiomyopathies. We hypothesize that ACTC mutations affecti ng sarcomere contraction lead to FHC and that mutations affecting force tra nsmission from the sarcomere to the surrounding syncytium lead to IDC.