Weber-Cockayne亚型单纯型大疱性表皮松解症一家系报告

目的:研究Weber-Cockayne亚型单纯型大疱性表皮松解症(EBS-WC)一家系的基因突变,并进行产前诊断。方法:应用PCR及DNA直接测序方法明确突变位点,针对所发现的突变以限制性内切酶片段长度多态性(RFLP)分析加以验证,在此基础上于妊娠24周时对从胎儿羊水所提取的DNA进行测序及酶切验证。结果:该家系患者存在角蛋白(keratin,KRT)5基因突变:第7外显子第1388位碱基由胸腺嘌呤突变为胞嘧啶,导致第463位氨基酸由亮氨酸变为脯氨酸(L463P)。50名健康对照者不存在此突变。羊水细胞DNA不存在此突变的胎儿,出生后未患大疱性表皮松解症。结论:KRT5第7外显子的突变是引起该家系临床症状的特异性突变。

Investigation of gene mutation in a family with Weber-Cockayne type epidermolysis bullosa simplex

Objective:To identify gene mutation in a family with Weber-Cockayne type epidermolysis bullosa simplex(EBS-WC).Methods:All exons of KRT5 and KRT14 gene were analyzed by PCR-DNA sequencing in the pedigree.The mutation was confirmed by restriction fragment length polymorphism(RFLP).Fetal DNA,extracted from amniotic fluid,was analysed for the mutation.Results:A missense mutation of T1388C was found which caused L463P substitution in exon 7 of keratin 5.The mutation was not found in 50 normal controls.The DNA sample in amniotic fluid was found to be normal.A healthy baby was born.Conclusions:The missense mutation L463P of keratin 5 is the underlying cause for this family with Weber-Cockayne type epidermolysis bullosa simplex(EBS-WC).