Schott J J, Benson D W, Basson C T, Pease W, Silberbach G M, Moak J P, Maron B J, Seidman C E, Seidman J G
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Science. 1998 Jul 3;281(5373):108-11. doi: 10.1126/science.281.5373.108.
Mutations in the gene encoding the homeobox transcription factor NKX2-5 were found to cause nonsyndromic, human congenital heart disease. A dominant disease locus associated with cardiac malformations and atrioventricular conduction abnormalities was mapped to chromosome 5q35, where NKX2-5, a Drosophila tinman homolog, is located. Three different NKX2-5 mutations were identified. Two are predicted to impair binding of NKX2-5 to target DNA, resulting in haploinsufficiency, and a third potentially augments target-DNA binding. These data indicate that NKX2-5 is important for regulation of septation during cardiac morphogenesis and for maturation and maintenance of atrioventricular node function throughout life.
编码同源框转录因子NKX2-5的基因突变被发现可导致非综合征性人类先天性心脏病。一个与心脏畸形和房室传导异常相关的显性疾病位点被定位到5号染色体长臂35区，果蝇tinman同源基因NKX2-5就位于该区域。已鉴定出三种不同的NKX2-5突变。其中两种预计会损害NKX2-5与靶DNA的结合，导致单倍剂量不足，第三种可能会增强靶DNA的结合。这些数据表明，NKX2-5对于心脏形态发生过程中的分隔调节以及整个生命过程中房室结功能的成熟和维持很重要。
