中文摘要：

目的分别研究一个先天性厚甲症Ⅰ型家系和一个散发患者基因突变，探讨基因型与表型的相关性。方法研究对象包括6例先天性厚甲症Ⅰ型患者，其中包括家系中5例患者和1例散发病例，同时取家系中1名正常人及与该家系无关的100名正常人作为正常对照排除多态性，采用长链PCR特异扩增了外周血基因组DNA的KRT16和KRT6A两个候选致病基因全长，PCR产物直接测序检测突变。结果家系和散发病例的KRT16基因均未发现基因突变。而两者的KRT6A基因分别出现了突变：家系中5例患者的第465位密码子由TAC突变为CAC，导致酪氨酸由组氨酸替代（Y465H）；散发患者KRT6A基因第171位密码子由AAC突变为GAC，导致天门冬酰胺由天门冬氨酸替代（N171D），而该家系中的1名正常人及与该家系无关的100名正常人的DNA测序结果未发现此突变。Y465H和N171D分别位于2B的终末端和1A的起始部这两个突变热点。结论该家系和散发病例分别存在KRT6A基因突变Y465H和N171D，其中前者为一新的错义突变，N171D近期已有文献报道。该突变可能为先天性厚甲症Ⅰ型的遗传病因。

英文摘要：

Objective To investigate the gene mutation in a Chinese pedigree and one sporadic case with pachyonychia congenita type Ⅰ（PC 1）, as well as to explore the relationship between the genotype and phenotype. Methods The whole coding region of the KRT16 and KRT6A genes were amplified by longrange polymerase chain reaction （PCR）. Six patients with PC-1 were studied, five of them were from a pedigree and the other one was sporadic. One unaffected member in the pedigree and 100 unrelated healthy individuals were also studied in order to exclude polymorpbism. PCR products were directly sequenced to detect the mutation. Results No mutations in the KRT16 gene were observed. All patients harbored a mutation in the KRT6A gene. All five patients in the pedigree had a mutation at eodon 465 （TAC to CAC） which substitutes tyrosine （Y） by histidine （H）. In the sporadic patient, codon 171 （AAC） was mutated to GAC, which changes the asparagines （N） to aspartic acid （D）. No such mutations were found in the unaffected member of the pedigree and the 100 unrelated controls. The mutation of Y465H is located at the end of 2B and N171D at the beginning of 1A domain of KRT6A, both are hotspots for pathogenic keratin mutations. Conclusion The mutations Y465H and N171D of the KRT16A gene were detected in the pedigree and the sporadic case respectively. The Y465H mutation was a novel mutation, and the N171D mutation was reported recently.