先天性厚甲症-1型基因突变分析

Identification of mutations in Chinese patients with pachyonychia congenita type 1

目的对2家系和1例散发的先天性厚甲症1型患者进行基因突变检测,为产前诊断和遗传咨询提供依据。方法采用巢式PCR扩增K6a基因突变热点区,通过DNA直接测序的方法,对先天性厚甲症患者、家系中的正常对照和100例无亲缘关系的正常人进行K6a突变检测。结果在K6a基因上发现3个错义突变(K6a1387G>C,K6a1393T>C,K6a513C>A),其中K6a1387G>C,K6a1393T>C为首次报道,而家系中正常对照和家系外100例正常人均未发现上述突变。结论K6a1387G>C,K6a1393T>C,K6a513C>A突变,不是罕见的单核苷酸多态,是导致患者发病的主要原因。中国人汉族患者与其他已研究的种族或民族有相似的突变热点区,但目前尚未发现基因型和表型之间的明确相关性。

Objective To detect the K6a gene mutation in two family and a sporadic Chinese patient with Pachyonychia Congenita type 1 （PC-1） and to explore the relationship between the genotype and phenotype of PC-1. Methods To detect the mutation in ＇ hot-spot＇ of the K6a gene by nested PCR and sequencing in PC-1 patients and 100 normal controls. Results We identified three missense mutations （ K6a 1387G 〉 C, 1393T 〉 C, 513C〉 A, two of them 1387 G〉C, 1393T〉C are novel） in the helix 1 A and 2B domain of the K6a polypeptide , but did not find in the healthy individuals from family and 100 unrelated normal individuals. Conclusion The three missense mutations （K6a 1387G〉C, 1393T〉C, 513C〉A） in the K6a gene are not rare single nucleotide polymorphisms（SNPs） seems to be the pathogenic cause in all affected individuals.