NKX2.5基因突变在先天性心脏病发病机制中的研究进展

Advance of NKX2.5 Gene Mutation in Pathogenesis of Congenital Heart Disease

NKX2.5/CSX基因的突变造成多种形态的先天性心脏病(congenital heart disease,CHD),是目前研究最多的与心脏发育密切相关的转录因子基因之一。NKX2.5基因的生殖细胞突变,目前已经发现29种,分别为无义突变、错义突变、缺失等,导致NKX2.5蛋白与DNA结合功能下降或失活,在先心病发病中占据重要位置。最近研究发现,在复杂型先心病中存在多种NKX2.5基因的体细胞突变,多个体细胞突变可能在先心病发病中起叠加效应。

The homeodomain （HD） protein NKX2.5, one of the key transcription factors required for the differentiation of mesodermal progenitor cells. It is a conserved transcription factor required for the organogenesis of the heart. Twenty-nine different heterozygous germline NKX2. 5 mutations have been identified in patients suffering from different congenital heart diseases （CHD）, which leads to either inactivation or reduction the combination of NKX2.5 protein and DNA. Recently somatic NKX2. 5 mutations as a novel mechanism of complex congenital heart disease are reported. The additive effect of sereral and somatic mutations may cause CHD.