CAJ | 학술논문

目的探讨激活T细胞核因子1(NFATC1)基因在人类单纯性先天性心脏病患者中的突变情况.方法应用聚合酶链反应(PCR)结合DNA测序技术,在56个单纯性先天性心脏病核心家系126例成员以及33例非先天性心脏病对照者中检测NFATC1基因IPT-NFAT区域的突变情况.结果 PCR扩增发现有58%(37/64)的患者以及74%(46/62)的患者一级亲属出现了2条电泳带,经测序证实2条带均为外显子7的扩增产物,分子量偏大的条带较正常的内含子区域的二倍重复序列(2×44 bp,4个单核苷酸多态性)多一个重复序列,成为三倍体(3×44 bp,6个单核苷酸多态性)重复序列.室间隔缺损、房间隔缺损以及主动脉瓣二叶畸形3类患者三倍体纯合子基因型频率为13.04%,而非先天性心脏病对照者及其他类型的先天性心脏病患者无三倍体纯合子基因型.并且主动脉瓣二叶畸形的患者其内含子的第3组重复序列的第17位碱基发现点突变(G→A).结论 NFATC1基因与人类的心内膜垫、膜隔和动脉瓣的发育有关,可能是一种潜在的导致室间隔缺损、房间隔缺损、主动脉瓣二叶畸形的易感基因.
목적 탐토격활T세포핵인자1(NFATC1)기인재인류단순성선천성심장병환자중적돌변정황.방법 응용취합매련반응(PCR)결합DNA측서기술,재56개단순성선천성심장병핵심가계126례성원이급33례비선천성심장병대조자중검측NFATC1기인IPT-NFAT구역적돌변정황.결과 PCR확증발현유58%(37/64)적환자이급74%(46/62)적환자일급친속출현료2조전영대,경측서증실2조대균위외현자7적확증산물,분자량편대적조대교정상적내함자구역적이배중복서렬(2×44 bp,4개단핵감산다태성)다일개중복서렬,성위삼배체(3×44 bp,6개단핵감산다태성)중복서렬.실간격결손、방간격결손이급주동맥판이협기형3류환자삼배체순합자기인형빈솔위13.04%,이비선천성심장병대조자급기타류형적선천성심장병환자무삼배체순합자기인형.병차주동맥판이협기형적환자기내함자적제3조중복서렬적제17위감기발현점돌변(G→A).결론 NFATC1기인여인류적심내막점、막격화동맥판적발육유관,가능시일충잠재적도치실간격결손、방간격결손、주동맥판이협기형적역감기인.
Objective To elucidate association between the mutation of nuclear factor of activated T cells 1 ( NFATC1 ) gene in IPT-NFAT region and simple congenital heart disease (CHD) in children. Method We used polymerase chain reaction (PCR) and the sequencing reaction to detect the mutations on the patients and their parents and (or) siblings. Results PCR amplification of the exon 7 region showed that 2 bands are obtained in 58% of patients with CHD and in 74% 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 ventricular septal defect (2/24), atrial septal defect (3/18) and bicuspid aortic valve (1/4) in which G to A transition at nucleotide 17 of the third 44 bps was found. Neither the unrelated non-CHD individuals nor the ones with other CHD showed positive presence for the homozygous form of this allele. Conclusions There is a differential amplification of a tandem repeat region in intron 7 of NFATC1 and homozygous form of this allele in patients with ventricular septal defect, atrial septal defect and bicuspid aortic valve. NFATC1 gene may be an a susceptibility marker for ventricular septal defect, atrial septal defect and bicuspid aortic valve.