title: Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.
abstract: We identified the alpha-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, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser 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 for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.
mesh_terms: D000199:Actins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009200:Myocardial Contraction / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D011487:Protein Conformation