一显性营养不良型大疱性表皮松懈症家系COL7A1基因突变分析
Analysis of COL7A1 gene mutation in a dominant dystrophic epidermolysis bullosa family

目的:检测一常染色体显性遗传营养不良型大疱性表皮松懈症(DEB)家系的COL7A1基因突变情况。方法:采用PCR技术和直接测序法分析该家系成员COL7A1基因全部外显子及内含子序列,并与50名健康个体及GenBank数据库中序列进行比较分析,筛选有意义突变。结果:在该家系COL7A1基因上共发现了5个突变位点,包括1个插入突变、1个错义突变和3个同义突变。COL7A1基因第13 号外显子上存在1个插入突变c.1731_1732insA,造成编码区阅读框架的移位,最终导致蛋白终止密码的产生。COL7A1基因第73号外显子上第6 016位的G错义突变为A,即c.6016G→A(p.G2006S)。其余3个同义突变分别为COL7A1基因上的c.1641G→T、c.5451 A→G和c.5508G→C。结论:COL7A1基因的插入突变c.1731_1732insA和错义突变c.6016G→A(p.G2006S)可能是该DEB家系患者临床表型的病因,其中c.1731_1732insA为新发突变。
Aim: To detect the mutations of COL7A1 gene in an autosomal dominant dystrophic epidermolysis bullosa(DEB)family.Methods: All exons and introns of COL7A1 gene in the family were detected by PCR technology and direct sequencing, and the obtained date were compared with 50 healthy individuals and Genbank sequence.Results: In total, five mutations in COL7A1 gene included one insert mutation, one missense mutation and three silent variations. A novel insert mutation(c.1731_1732insA)at the 13th exon of COL7A1 was found, which caused a shift in the reading frame and resulted in premature termination condon(PTC). A missense mutation(c.6016G→A, p.G2006S)was observed at the 73rd exon of COL7A1 gene. The other three silent mutations included c.1641G→T, c.5451A→G and c.5508G→C.Conclusion: The mutation c.1731_1732insA and c.6016G→A(p.G2006S)of COL7A1 gene may be responsible for the phenotype of DEB, and the c.1731_1732insA is a novel mutation