Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy.
Idiopathic dilated cardiomyopathy is a common cause of heart failure. Half of cases are believed to be hereditary, and mutations in cardiac sarcomeric contractile protein genes have been reported with autosomal dominant inheritance. We used mutation analysis suitable for identification of both dominant and recessive mutations to investigate the sarcomeric gene for cardiac troponin I (TNNI3) in 235 patients with dilated cardiomyopathy. We identified a novel TNNI3 mutation in a family with recessive disease. Functional studies showed impairment of troponin interactions that could lead to diminished myocardial contractility. TNNI3 is the first recessive gene identified for this condition, and we suggest that other such genes could be pinpointed by mutation analyses designed to identify homozygous mutations.
Murphy
Ross T
RT
Department of Cardiological Sciences, St George's Hospital Medical School, London, UK.
Mogensen
Jens
J
Shaw
Anthony
A
Kubo
Toru
T
Hughes
Sian
S
McKenna
William J
WJ
D000328:Adult; D019943:Amino Acid Substitution; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D019210:Troponin I / Q000235:genetics*
D019210:Troponin I