角蛋白14突变导致Dowling-Meara亚型单纯型大疱性表皮松解症伴色素沉着

A mutation of KRT14 gene in a patient with Dowling-Meara type epidermolysis bullosa simplex with pigmentation

目的:检测Dowling-Meara亚型单纯型大疱性表皮松解症(DM-EBS)伴色素沉着一家系的基因突变。方法:收集DMEBS患儿临床资料;取皮损行透射电镜检查;应用PCR及DNA直接测序的方法,检测该家系成员角蛋白(KRT)5和KRT14基因的全部编码序列,并与正常序列进行对比。结果:透射电镜检查可见基底细胞下部裂隙形成,张力微丝呈团块状。患儿KRT14基因第1号外显子中的第373位碱基发生C→T杂合突变(c.C373 T),导致其编码的KRT14 1A螺旋段第125位氨基酸发生错义突变(p.R125C),患儿父母未发现该突变。结论:KRT14基因的R125C突变可能为引起该患儿临床表型的病因,推测认为该突变不仅可引起表皮松解,还可造成皮肤色素沉着。

Objective：To determine the gene mutation in a family with Dowling-Meara type epidermolysis bullosa simplex with pigmentation. Methods：Transmission electron microscopy study was performed. The encoding regions of keratin 5 and keratin 14 were analyzed by PCR and direct DNA sequencing, and compared the sequences in this family with the sequence from gene database. Results： Transmission electron microscopy revealed formation of intraepidermal blister and severe keratin filament clumping. A heterozygous missense mutation （c.C373T） was detected,which led to the replacement of the normal arginine codon （CGC） with a cysteine codon （TGC） at position 125 of the resultant protein（p.R125C）. The mutation was not detected in his unaffected parents. Conchlsion： Mutation of R125C of KRT14 gene may be the cause of the clinical phenotype of this patient. This mutation may cause epidermolysis and pigmentation.