二例遗传性大疱性表皮松解症基因突变研究

目的:检测分析2例遗传性大疱性表皮松解症患者致病基因及突变位点。方法:收集患者资料,提取患者及父母外周血DNA,利用全基因组外显子测序筛查致病基因,经生物信息学分析获得致病变异;随后用Sanger测序在患者及其亲属中验证该突变。结果:患者1父母表型正常,患者2父亲有相似临床表现。患者1携带COL7A1基因73号外显子c.6082G>A(p.G2028R)的错义突变,其父母未发现该突变。患者2及其父亲携带2个致病的错义突变,即COL7A1基因c.6235G>A(p.G2079R)突变和KRT5基因c.499G>A(p.E167K)突变,其母未发现该突变。结论:散发患者存在的COL7A1基因突变属于新生突变;患者2及其父亲同时携带COL7A1基因和KRT5基因的杂合错义突变,为国内外首次报道。

Gene mutation in inherited epidermolysis bullosa in 2 cases

Objective: To detect and analyze the pathogenic genes and mutation sites in two patients with inherited epidermolysis bullosa. Methods: The data of two patients were investigated and DNA was extracted in peripheral blood samples from patients and their parents. The whole-exome sequencing was performed to screen pathogenic genes, and the sequencing results were analyzed by bioinformatics to obtain pathogenic candidate mutations. The mutations also verified by Sanger sequenced in patients and their relatives. Results: The parents of the first patient had normal phenotypes, and the father of the second patient had the manifestations of inherited epidermolysis bullosa. A missense mutation of c.6082G>A (p.G2028R) in exon 73 of COL7A1 gene was detected in the first sporadic patient, which was not found by her parents. Two pathogenic missense mutations, C.6235G>A (p.G2079R) mutation in the COL7A1 gene and C.499G>A (p.E167K) mutation in the KRT5 gene were found in the second patient and his father. Conclusion: The COL7A1 gene mutation in sporadic patient is a de novo mutation. One patient in a pedigree carried two missense mutations of COL7A1 gene and KRT5 gene is the first report at home and abroad.