三个X-连锁重症联合免疫缺陷病家系的IL2RG基因新突变及产前诊断

Mutation analysis and prenatal diagnosis of three families with X-linked severe combined immunodeficiency

目的:对3个X-连锁重症联合免疫缺陷病(SCID)家系进行致病基因突变分析和产前诊断。方法:收集2017~2018年于深圳市妇幼保健院医学遗传中心就诊的3个X-SCID家系中先证者及家庭成员的外周血,提取DNA,应用高通量测序和Sanger测序筛查三个家系IL2RG基因的突变位点,并分析突变位点的致病性,继而对家系中的高危胎儿进行产前诊断。结果:共发现IL2RG基因3个致病突变,均未见报道。3个X-SCID家系分别发现IL2RG基因:c.272dupA(p.Tyr91*),c.245_246insC(p.P82Pfs*15)和c.507delG(p.Q169fs*170)突变。结论:IL2RG基因突变:c.272dupA(p.Tyr91*),c.245_246insC(p.P82Pfs*15)和c.507delG(p.Q169fs*170)分别是3个家系的发病原因。高通量测序结合Sanger测序对X-SCID的基因诊断具有重要的价值。

Objective:To evaluate mutation analysis and prenatal diagnosis for 3 families with a birth history of X- linked severe combined immunodeficiency (X-SCID). Methods:Blood samples of a male infant patient of X-SCID and his family members' were collected.Next generation sequencing and Sanger sequencing were performed to assess the pathogenic mutation.Prenatal genetic diagnoses were performed by after the genotypes of maternal probands were identified. Results:Three mutations (c.272dupA(p.Tyr91*),c.245_246insC ( p.P82Pfs *15 ),c.507delG(p.Q169fs*170)of IL2RG gene were identified in these three families respectively.The probands in the three families carry the corresponding mutant hemizygotes,and the mothers carry the corresponding mutant heterozygotes. Conclusions:Three novel mutations in IL2RG gene c.272dupA(p.Tyr91*),c.245_246insC (p.P82Pfs *15), c.507delG (p.Q169fs*170)may be the pathologic cause of the probands with X-SCID of the 3 families respectively.Next generation sequencing combining Sanger sequencing is a strategy for mutation analysis and prenatal diagnosis of X- SCID.