14例眼皮肤白化病Ⅱ型患者P基因变异分析

Analysis of P gene variations among fourteen patients with oculocutaneous albinism type Ⅱ

目的对14例临床拟诊眼皮肤白化病(oculocutaneous albinism,OCA)患者及核心家系TYR及P基因进行变异分析,为家系的遗传咨询及产前诊断提供依据.方法应用直接测序的方法对患者及家系成员进行TYR及P基因变异检测,寻找可能的致病变异位点,对新发现的变异采用SIFT及PolyPhen-2生物信息学软件进行蛋白功能预测.结果测序结果显示TYR基因筛查均未检出变异,P基因共检出了9种变异类型,26个变异位点,分别为c.803-3C>G(7/26)、c.1327G>A(p.Val443Ile)(5/26)、c.632C>T(p.Pr0211Leu)(4/26)、c.1832T>C(p.Leu611Pro)(3/26)、c.1349C>A(p.Thr450Lys)(2/26)、c.2363C>T(p.Ser788Leu)(2/26)、c.2228C>T(p.Pr0743Leu)(1/26)、c.1525A>G(p.Thr509Ala)(1/26)、c.1349C>T(p.Thr450Met)(1/26),其中2个家系只检出1个杂合位点.c.2363C>T(p.Ser788Leu)、c.1832T>C(p.Leu611Pro)、c.1525A>G(p.Thr509Ala)3个变异位点未见报道,蛋白功能预测均为有害变异.结论本地区眼皮肤白化病以Ⅱ型为主,P基因以c.803-3C>G和c.1327G>A(p.Va1443Ile)变异最为常见,新变异的发现丰富了P基因的变异谱.

Objective To analyze variations of TYR and P genes among 14 patients with clinically diagnosed oculocutaneous albinism.Methods Potential variations of the TYR and P genes were detected by Sanger sequencing.Novel variations were predicted with bioinformatics software including SIFT and PolyPhen-2.Results No variation was found in the TYR gene,while 9 types of variations were found in the P gene among the 14 patients,which included c.803-3C>G(7/26),c.1327G>A(p.Val443Ile)(5/26),c.632C>T(p.Pro211Leu)(4/26),c.1832T>C(p.Leu611Pro)(3/26),c.1349C>A(p.Thr450Lys)(2/26),c.2363C>T(p.Ser788Leu)(2/26),c.2228C>T(p.Pro743Leu)(1/26),c.1525A>G(p.Thr509Ala)(1/26),and c.1349C>T(p.Thr450Met)(1/26).Only 1 heterozygous variation was detected in 2 families.c.2363C>T(p.Ser788Leu),c.1832T>C(p.Leu611Pro)and c.1525A>G(p.Thr509Ala)were not reported previously and predicted as"harmful"to the protein function.Conclusion The main type of ocular albinism is oculocutaneous albinism typeⅡin Liuzhou region,where the most common variations of the P gene were c.803-3C>G and c.1327G>A(p.Val443Ile).Above finding has enriched the variation spectrum of the P gene.