胫前显性营养不良型大疱性表皮松解症基因突变研究

Mutation analysis of the COL7A1 gene in pretibial dominant dystrophic epidermolysis bullosa

目的探讨Ⅶ型胶原基因（COL7A1）在胫前显性营养不良型大疱性表皮松解症（DDEB—Pt）发病中的意义。方法收集中国汉族1例DDEB—Pt散发患者及其家庭成员和100例健康对照的外周血标本，用改良盐析法提取外周静脉血中的基因组DNA，通过PCR反应扩增和测序进行序列分析。结果测序结果显示，COL7A1基因73号外显子的第6109位碱基鸟嘌呤（G）转化为腺嘌呤（A），使得三螺旋区第2037位密码子由GCT变成ACT，编码氨基酸由甘氨酸（Gly）变为精氨酸（Arg），即c．G6109A（p．Gly2037Arg）甘氨酸替换突变。结论COL7A1基因甘氨酸替换突变为致病性突变，是一新发突变。

Objective To explore the role of type VlI collagen （COL7A1） gene in the pathogenesis of pretibial dominant dystrophic epidermolysis bullosa （DDEB-Pt）. Methods Peripheral blood samples were obtained from a sporadic Chinese patient of Han nationality with DDEB-Pt, his parents and 100 healthy human controls. A modified salting-out method was used to extract genomic DNA from the blood samples, and PCR was performed to amplify 118 exons of the COL7A1 gene followed by DNA sequencing. Results A G→A mutation was identified at position 6109 （G6109A） in exon 78 of the COL7A1 gene in this patient, which caused a change from CCT to ACT at codon 2037 in the triple helix region, and resulted in the substitution of glycine （Gly） by arginine （Arg） （p.Gly2037Arg）. Conclusion A novel glyeine substitution mutation was identified in the COL7A1 gene in the patient with DDEB-Pt, which may be a pathogenic mutation.