COL7A1与PLEC双基因突变致大疱性表皮松解症一例国内首报

【摘要】 目的 对1例营养不良型大疱性表皮松解症患儿家系进行基因突变分析。方法 收集1例营养不良型大疱性表皮松解症患儿临床资料，提取患儿及其父母外周血DNA进行全基因组外显子测序，将测序结果与既往报道的大疱性表皮松解症基因进行比对，比对结果采用Sanger测序方法进行验证并预测生物学信息，在100例健康对照中验证该位点。结果 患儿存在复合杂合突变，共携带3个致病突变，即COL7A1基因c.3625_3635 del11、c.6270delT突变和PLEC基因c.12772G＞A突变。其中COL7A1基因c.6270delT突变和PLEC基因c.12772G＞A突变皆为新发突变。COL7A1基因c.3625_3635 del11及c.6270delT突变来自父亲，导致肽链合成提前终止，产生截短蛋白；PLEC基因c.12772G＞A突变来自母亲，导致网蛋白第4258位谷氨酸被赖氨酸替代（p.Glu4258Lys）。结论 该患儿是由COL7A1与PLEC双基因突变所致的常染色体隐性遗传营养不良型大疱性表皮松解症。

A case of epidermolysis bullosa caused by mutations in the COL7A1 and PLEC genes firstly reported in China

Objective To detect gene mutations in a patient with dystrophic epidermolysis bullosa and his family.Methods Clinical data were collected from a child with dystrophic epidermolysis bullosa,and DNA was extracted from peripheral blood of the patient and his parents for whole-exome sequencing.The sequencing result was compared with previously reported sequences of genes related to dystrophic epidermolysis bullosa,the comparison results were verified by Sanger sequencing,and biological information was predicted.The mutations were also verified in 100 healthy controls.Results Compound heterozygous mutations were identified in the patient,including 3 pathogenic mutations,namely c.3625_3635 del11 and c.6270delT mutations in the COL7A1 gene and c.12772G>A mutation in the PLEC gene.The c.6270delT mutation in the COL7A1 gene and c.12772G>A mutation in the PLEC gene were novel mutations.The c.3625_3635 del11 and c.6270delT mutations in the COL7A1 gene were inherited from the patient′s father,which led to premature peptide chain termination,producing a truncated protein;the c.12772G>A mutation in the PLEC gene was inherited from the patient′s mother,resulting in substitution of glutamic acid by lysine at amino acid position 4258 of plectin(p.Glu4258Lys).Conclusion Digenic mutations in the COL7A1 and PLEC genes were responsible for autosomal recessive dystrophic epidermolysis bullosa in the patient.