两个疑似眼皮肤白化病家系的基因突变分析  

Mutation analysis of two pedigrees with suspected oculocutaneous albinism

作　　者：叶海昀[1] 兰小平 乔彤[1] 许无恨[2] 汤晓君 杨永臣[2] 张泓[2] Ye Haiyun;Lan Xiaoping;Qiao Tong;Xu Wuhen;Tang Xiaojun;Yang Yongchen;Zhang Hong(Department of Ophthalmology Shanghai Children’s Hospital, Children’s Hospital of Shanghai Jiao Tong University, Shanghai, 200062, China;Molecular Diagnostic Laboratory, Shanghai Children’s Hospital, Children’s Hospital of Shanghai Jiao Tong University, Shanghai, 200062, China)

机构地区：[1]上海市儿童医院上海交通大学附属儿童医院眼科,200062 [2]上海市儿童医院上海交通大学附属儿童医院临床分子实验室,200062

出　　处：《中华医学遗传学杂志》2019年第3期212-216,共5页Chinese Journal of Medical Genetics

基　　金：上海市卫计委重要薄弱学科建设项目(2015ZB0203);上海市儿童医院面上项目(2016YMS001).

摘　　要：目的对2个疑似眼皮肤白化病家系进行基因分析,为临床确诊分型、遗传咨询及产前诊断提供依据。方法采用包含白化病相关基因的二代测序Panel结合Sanger测序验证的方法对2个家系成员的外周血基因组DNA进行检测,并根据美国医学遗传学与基因组学学会标准对突变进行了致病性分析。结果家系1在TYR基因中检测到c.896G>A和c.819+3insATATGCC两个杂合突变,二者为复合杂合突变,其中c.819+3insATATGCC的致病性尚未见报道,软件预测该突变可通过影响外显子的正常剪接而致病。家系2在OCA2基因中检测到c.727C>T和c.1870G>C两个杂合突变,二者同样为复合杂合突变,c.1870G>C的致病性未见报道,但软件预测其为有害突变。结论两个疑似眼皮肤白化病家系分别是由TYR基因和OCA2基因的复合杂合突变所引起的Ⅰ型和Ⅱ型OCA,并各检测到一个未见报道的致病新变异,进一步丰富了白化病基因突变数据库。Objective To analyze the clinical presentation and gene of 2 pedigrees with suspected oculocutaneous albinism(OCA), and provide basis for clinical classification, genetic counseling and prenatal diagnosis. Methods Variants were identified using next-generation sequencing(NGS) and confirmed by Sanger sequencing in 2 pedigrees with suspected OCA. The pathogenicity of the variants was analyzed according to the American College of Medical Genetics and Genomics (ACMG) standard. Results Two compound heterozygous mutations of TYR and OCA2 genes were identified respectively in 2 pedigrees with suspected OCA. The mutation of c. 819+ 3insATATGCC in TYR and the mutation of c. 1870G>C in OCA2 are first reported in this study. The pathogenicity analysis shows that two novel mutations are likely pathogenic by combination of prediction of SIFT, Polyphen-2 and Human Splicing Finder. Conclusion The findings of this study expand the mutational spectrum of OCA. Compound heterozygous mutations in the TYR and OCA2 gene may be responsible for clinical manifestations of 2 pedigrees with suspected OCA.

关 键 词：眼皮肤白化病 二代测序 TYR基因 OCA2基因 致病性 

分 类 号：R725.9[医药卫生—儿科] R440[医药卫生—临床医学]