Graduate School, Peking Union Medical College, Beijing, China.
Hum Genet. 2011 Nov;130(5):657-62. doi: 10.1007/s00439-011-0996-7. Epub 2011 May 5.
IRX4 was the first identified cardiac transcription factor that is restricted to the ventricles at all stages of heart development. Irx4-deficient mice show ventricular dysfunction and develop cardiomyopathy. To study the potential impact of sequence variations in IRX4 on congenital heart disease (CHD) in humans, we examined the coding region of IRX4 in a cohort of 698 Chinese people with congenital heart disease and 250 healthy individuals as the controls. We found two potential disease-causing mutations, p. Asn85Tyr and p. Glu92Gly. A mammalian two-hybrid assay showed that both of the mutations significantly affected the interaction between IRX4 and RXRA. It demonstrated that IRX4 had a potential causative impact on the development of congenital heart disease, particularly ventricular septal defect.
IRX4 是第一个被鉴定的心脏转录因子，它在心脏发育的所有阶段都局限于心室。Irx4 缺陷型小鼠表现出心室功能障碍，并发展为心肌病。为了研究 IRX4 序列变异对人类先天性心脏病 (CHD) 的潜在影响，我们在一个由 698 名先天性心脏病患者和 250 名健康个体组成的队列中检查了 IRX4 的编码区。我们发现了两个潜在的致病突变，p.Asn85Tyr 和 p.Glu92Gly。哺乳动物双杂交试验表明，这两个突变都显著影响了 IRX4 和 RXRA 之间的相互作用。这表明 IRX4 对先天性心脏病，特别是室间隔缺损的发展有潜在的致病影响。
