眼皮肤白化病分型及珊基因新突变的鉴定

目的了解我国眼皮肤白化病（oculocutaneous albinism，OCA）的分型和相关基因突变类型，探讨新突变可能的分子致病机制。方法应用PCR方法扩增TYR基因，经DNA序列测定检出突变，采用错配引物PCR进行新突变的群体筛查，结合生物信息学方法探讨一种新突变的致病性和可能的分子致病机制。结果10名患者中有5人存在2个突变TYR等位基因，共计8种突变类型，其中c．71G〉A（C24Y）和c．841G〉T（E281X）是OCA1A致病性新突变；C24极可能参与二硫键形成，C24Y将导致酪氨酸酶肽链内此二硫键消失，进而引起蛋白空间构象变化和功能异常而致病。结论从基因水平初步了解了我国OCA1所占的比例，探讨了TYR基因C24Y的致病性并初步阐明了其致病的分子机制。本结果丰富了人类TYR基因突变类型，为我国OCA分型诊断、产前基因诊断和遗传咨询等积累了有价值的数据资料。

Classification of Oculocutaneous Albinism and Identification of a Novel TYR Gene Mutation

Objective To understand the category of oculocutaneous albinism （OCA） and OCA related gene mutation subtypes in China. Methods A study on tyrosinase （TYR） gene mutation in OCA patients was conducted by DNA sequencing and multiple molecular biology techniques. Results The results showed that 5 of 10 patients had two mutated TYR genes, counting up to eight types of mutations in total. Among the mutations, c. 71G 〉 A （C24Y） and c. 841G 〉 T （E281 X） were found to be novel pathogenic mutations. It was predicted by bioinformatics methods that C24 likely participates in the formation of disulfide bonds. Therefore, C24Y may result in loss of disulfide bond of peptide chain in tyrosinase and further cause disease due to protein conformation change and dysfunction. Conclusion The results not only revealed the mutation types of the human TYR genes, but also provided valuable data for researches pertaining to molecular diagnosis of OCA and genetic counseling.