Actin mutations in dilated cardiomyopathy, a heritable form of heart failure.
To test the hypothesis that actin dysfunction leads to heart failure, patients with hereditary idiopathic dilated cardiomyopathy (IDC) were examined for mutations in the cardiac actin gene (ACTC). Missense mutations in ACTC that cosegregate with IDC were identified in two unrelated families. Both mutations affect universally conserved amino acids in domains of actin that attach to Z bands and intercalated discs. Coupled with previous data showing that dystrophin mutations also cause dilated cardiomyopathy, these results raise the possibility that defective transmission of force in cardiac myocytes is a mechanism underlying heart failure.
Olson
T M
TM
Department of Pediatrics, Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA. timo@howard.genetics.utah.edu
Michels
V V
VV
Thibodeau
S N
SN
Tai
Y S
YS
Keating
M T
MT
D000199:Actins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D005091:Exons; D005260:Female; D006321:Heart / Q000503:physiopathology; D006801:Humans; D008297:Male; D009154:Mutation; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011487:Protein Conformation; D012518:Sarcomeres / Q000502:physiology
D000199:Actins