眼皮肤白化病基因一种可疑致病突变二例

摘要

目的 对两对曾生育白化病患儿的夫妇进行非综合征型眼皮肤白化病Ⅰ～Ⅳ型和眼白化病Ⅰ型相关基因的突变筛查,以了解携带者的突变类型.方法 对非综合征型白化病相关基因TYR、OCA2、TYRP-1、MITF、SLC45A2和GPR143各外显子进行深度测序,并通过Sanger测序验证结果.结果 两位女性携带者均在TYR基因编码区发现了1个框移突变c.925_926insC,分析其为可疑致病突变.一例男性携带者在TYR基因编码区发现1个无义突变c.832C＞T,为已知致病突变,另一例男性携带者则在其TYR基因的编码区发现了一种已知的致病无义突变c.346C＞T.结论 TYR基因编码区的c.925_926insC为OCA1型的可疑致病性框移突变.%Objective To detect potential mutations in genes related with non syndromic oculocutaneous albinism Ⅰ-Ⅳ and ocular albinism type Ⅰ in two couples who had given births to children with albinism.Methods All exons of the non-syndromic albinism related genes TYR,OCA2,TYRP-1,MITF,SLC45A2 and GPR143 were subjected to deep sequencing.The results were verified with Sanger sequencing.Results For the two female carriers,the coding region of the TYR gene was found to harbor a frameshift mutation c.925_926insC,which was also suspected to have been pathogenic.In one of the male partners,a nonsense mutations c.832C＞T was found,which was also known to be pathogenic.Another male partner was found to harbor a TYR gene mutation c.346C＞T,which was also known to be a pathogenic nonsense mutation.Conclusion The coding region of the TYR gene c.925_ 926insC (p.Thr309ThrfsX9) probably underlies the OCA1 disease phenotype.