KRT14基因突变伴KLHL24基因正常的中国汉族手足复发型大疱性表皮松解症一家系

A Weber-Cockayne Epidermolysis Bullosa Simplex Chinese Han Nationality with KRT14 Mutation and Normal KLHL24

目的对一个中国汉族手足复发型单纯型大疱性表皮松解症(Weber-Cockayne type epidermolytic bullosa simplex,EBS-WC)家系进行致病基因检测,探讨KLHL24基因和KRT14基因在EBS发病机制中的相关性,为产前诊断和遗传咨询提供依据。方法提取该家系中4例患者以及5例健康人外周血基因组DNA,扩增KRT5和KRT14基因的全部外显子,以及KLHL24基因的启动子,并测序。以寻常性银屑病外显子测序研究中的676例正常人群为对照。收集先证者皮损组织进行病理检查。结果先证者病理诊断支持单纯型大疱性表皮松解症。所有患者均出现KRT14基因第6外显子第1162位错义突变(c.1162C>T),导致388位胞嘧啶(C)被胸腺嘧啶(T)替换,角蛋白结构中精氨酸被半胱氨酸取代。家系中的正常人和676例无血缘关系的健康人没有发现相同的碱基改变。家系中没有发现KLHL24基因起始密码子突变。结论KRT14基因第6外显子的错义突变是该中国汉族EBS-WC家系患者的致病基因。

Objective To detect the gene mutation of patients in a Chinese Han pedigree with EBS-WC, and to discuss the relationship between KLHL24 and KRT14 in the pathogenesis of EBS. Methods Genomic DNA were extracted from perpheral blood samples of four patients and five healthy in the pedigree and 676 unrelated individuals, the exons of KRT5 ,KRT\4 and start-codon of KLHL24 were analyzed after amplified. Lesions of the proband was collected for pathological examnation. Results Pathological characteristics of the lesion supported the diagnosis. A heterozygous missense mutation (c. 1162C > T) was identified in the 1162 site of exon 6 of KRT14 in all 4 patients, which resulted in substitution of thymine for cytosine, and substitution of cysteine for arginine at position 388 of the KRT14 protein. No mutation was found in family healthy individuals and 676 unrelated individuals. No mutation was found in KLHL2A gene. Conclusion The missense mutation (c. 1162C > T) in the 1162 site of exon 6 of KRT14 gene is the pathogenic gene in this Chinese Han EBS-WC pedigree.