Murphy Ross T, Mogensen Jens, Shaw Anthony, Kubo Toru, Hughes Sian, McKenna William J
Department of Cardiological Sciences, St George's Hospital Medical School, London, UK.
Lancet. 2004 Jan 31;363(9406):371-2. doi: 10.1016/S0140-6736(04)15468-8.
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.
特发性扩张型心肌病是心力衰竭的常见病因。据信，半数病例为遗传性，且已有报道称心脏肌节收缩蛋白基因突变呈常染色体显性遗传。我们采用适用于鉴定显性和隐性突变的突变分析方法，对235例扩张型心肌病患者的心脏肌钙蛋白I（TNNI3）肌节基因进行了研究。我们在一个患有隐性疾病的家族中发现了一种新的TNNI3突变。功能研究表明肌钙蛋白相互作用受损，这可能导致心肌收缩力减弱。TNNI3是首个被鉴定出与该病相关的隐性基因，我们认为通过旨在鉴定纯合突变的突变分析，有可能找出其他此类基因。
