Yehya Amin, Souki Ramzi, Bitar Fadi, Nemer Georges
Department of Biochemistry, American University of Beirut (AUB), Bliss St., P.O. Box 110236, Beirut, Lebanon.
Genome. 2006 Sep;49(9):1092-8. doi: 10.1139/g06-072.
Most forms of congenital heart disease (CHD) result from aberrations in cardiac morphogenesis including errors in septation, valve formation, and proper patterning of the great vessels. Transcription factors are key proteins that dictate mRNA synthesis rate and subsequent protein production in most eukaryotes. NFATC1 belongs to the Rel family of transcription factors. In mice, it is expressed in the embryonic heart and is restricted to the endocardium where it plays a major role in valve formation. To establish a role for NFATC1 in CHD, we started screening for mutations in the exons encoding the DNA-binding domain of NFATC1 in patients enrolled in our study on CHD in Lebanon. DNA was extracted from patients with pulmonary stenosis (PS), tricuspid atresia (TA) and ventricular septal defect (VSD). PCR amplification and DNA sequencing were done on the patients and their parents and (or) siblings. PCR amplification of the exon 7 region showed that 2 bands are obtained in 57% of patients with CHD (32/56) and in 45% of their healthy parents and (or) siblings. Sequencing of the 2 bands revealed that both are amplicons of the exon 7 region, and that the additional band harbors an additional 44 nucleotides segment in the intronic region. The homozygous form of this allele was only present in patients with VSD (2/21). A screen of a pool of 81 healthy, unrelated individuals showed no presence for the homozygous form of this allele, suggesting that NFATC1 is a potential VSD-susceptibility gene.
大多数先天性心脏病（CHD）是由心脏形态发生异常引起的，包括间隔形成、瓣膜形成以及大血管正常模式的错误。转录因子是在大多数真核生物中决定mRNA合成速率和后续蛋白质产生的关键蛋白质。NFATC1属于转录因子的Rel家族。在小鼠中，它在胚胎心脏中表达，并局限于心内膜，在瓣膜形成中起主要作用。为了确定NFATC1在CHD中的作用，我们开始对参加黎巴嫩CHD研究的患者中编码NFATC1 DNA结合域的外显子进行突变筛查。从患有肺动脉狭窄（PS）、三尖瓣闭锁（TA）和室间隔缺损（VSD）的患者中提取DNA。对患者及其父母和（或）兄弟姐妹进行PCR扩增和DNA测序。外显子7区域的PCR扩增显示，57%的CHD患者（32/56）及其45%的健康父母和（或）兄弟姐妹中获得了两条带。对这两条带的测序显示，两者都是外显子7区域的扩增子，并且额外的带在内含子区域含有一个额外的44个核苷酸片段。该等位基因的纯合形式仅存在于VSD患者中（2/21）。对81名健康、无亲缘关系的个体进行的筛查显示，该等位基因的纯合形式不存在，这表明NFATC1是一个潜在的VSD易感基因。
