一先天性厚甲家系角蛋白基因突变鉴定

Identification of keratin gene mutations in a Chinese family with pachyonychia congenita

目的 探讨一个先天性厚甲家系角蛋白基因突变。方法 用PCR及Sanger测序技术对先天性厚甲家系先症者KRT17基因所有外显子和KRT6B基因编码螺旋起始和终止区域序列进行突变鉴定，针对发现的可疑位点，Sanger测序检测家系其他成员该位点的变异情况。结果 基因检测结果表明，家系患者KRT17基因错义突变c.263T 〉 C，该突变导致角蛋白17（K17）第88位氨基酸由蛋氨酸变成苏氨酸（p.M88T），KRT6B基因未见异常。结论 KRT17基因c.263 T 〉 C（p.M88T）突变是该先天性厚甲家系致病基因突变。

Objective To identify keratin gene mutation in a Chinese family with pachyonychia congenita （PC）. Methods Blood samples were collected from 2 patients and 4 unaffected family members in a Chinese family with PC. Genomic DNA extracted from the proband was subjected to the amplification of all exons and their intronic and flanking sequences of the KRT17 gene as well as the helix initiation and termination motifs of the KRT6B gene by PCR, followed by gene sequencing with the Sanger method. Then, the mutations of KRT17 and KRT6B genes detected in the proband were screened in the other family members. Results A missense mutation c.263 T 〉 C （p.M88T） in KRT17 gene, which results in a substitution of methionine （M） by threonine （T） at position 88 of the keratin 17, was observed in the 2 patients in this family. No mutation was found in the KRT6B gene in any of the family members or in the KRT17 gene in unaffected family members. Conclusion The missense mutation c.263T 〉 C （p.M88T） in KRT17 gene is likely to be a causative mutation of PC in this family.