中文摘要：

目的：对临床诊断为眼皮肤白化病（OCA）患者的酪氨酸酶（TYR）基因进行突变筛查，了解我国大陆OCA患者TYR基因突变类型，探讨基因突变对人TYR蛋白结构和功能的影响。方法：应用PCR技术，扩增患者及其父母的TYR基因外显子、外显子-内含子交界区及启动子区；以DNA序列测定技术，进行突变筛查与鉴定；利用生物信息学方法，对突变引起蛋白结构和功能的改变进行预测与分析。结果：在15名患者的30个TYR等位基因内，查明11种突变；其中错义突变5种（W400L、R299H、E294K、R77Q和K142M），无义突变3种（R116X、R278X和G295X），插入突变2种（929insC和232insGGG），剪切位点突变1种（IVS1-3 C〉G）；对4个突变W400L、R299H、929insC、232insGGG的生物信息学分析显示，突变的致病性与蛋白结构和功能的改变相关。结论：W400L占本研究所检出全部OCA1突变等位基因的30．0％（9／30），可能为中国大陆人群中较常见的TYR基因突变类型；应用生物信息学分析方法对TYR基因突变的致病性做出一些合理可能的解释是可行的。

英文摘要：

Objective： To explore the patients＇ genotypes and the mutation spectrum of Tyrosinase（TYR） gene and the effects on protein structure and function in oculocutaneous albinism type 1 （OCA1）. Methods： The polymerase chain reaction（PCR） and sequencing techniques were applied to amplify and analyze the regions of exon, exonintron and promoter of TYR gene of 15 OCA1 probands and some of their parents. The protein structure and function were forecasted and analyzed by bioinformatics software. Results： Sequencing result showed 11 kinds of mutations, including 5 missense mutatiom（W400L, R299H, E294K, R77Q and K142M）, 3 nonsense mutafions（R116X, R278X and G295X）, 2 insertion mutation（929insC and 232insGGG） and 1 splice site mutation（IVS1-3C 〉 G）. The nosogenesis was rdated to the change of protein structure and function in four pathological mutations. Conclusion： It seemes that W400L is the frequent mutations, which accounted for about 30.0% in Chinese mainland OCA1 alleles. It is doable to make some reasonable interpretation about TYR gene nosogenesis by bioinformatics method.