外显子测序联合Sanger测序行X-连锁重症联合免疫缺陷家系分析及产前诊断1例报告  

Application of exome sequencing combined with Sanger sequencing to pedigree analysis and prenatal diagnosis of X-linked severe combined immunodeficiency: a case report

作　　者：韦懿芸[1] 曾繁娟 庞丽红[1] 杨冬艳 WEI Yi-yun;ZENG Fan-juan;PANG Li-hong;YANG Dong-yan(Department of Prenatal Diagnosis and Genetic Diseases,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院产前诊断与遗传病诊断科

出　　处：《广西医学》2019年第14期1770-1773,共4页Guangxi Medical Journal

基　　金：广西自然科学基金(2018GXNSFAA281216)

摘　　要：目的探讨外显子测序联合Sanger测序应用于X-连锁重症联合免疫缺陷(X-SCID)家系分析及产前诊断的可行性。方法回顾性分析1例X-SCID先证者病史及家族史。用外显子测序技术对先证者免疫缺陷相关基因的外显子进行测序,捕获致病基因后,提取其父母外周血DNA,采用Sanger测序技术进行验证。确定先证者该致病基因遗传于其母亲后,其母亲再次妊娠9周时绒毛取样提取DNA并采用Sanger测序行产前诊断。结果外显子测序结果提示先证者X染色体白细胞介素2受体的γ共用链(IL2RG)基因存在错义突变(c.713G>A,p.Ser238Asn)。Sanger测序结果显示,先证者母亲该位点存在杂合突变,其父亲该位点未见异常。先证者母亲再次妊娠时胚胎绒毛组织X染色体IL2RG基因存在错义突变,诊断胎儿为X-SCID。结论应用外显子测序法捕获X-SCID的相关致病基因,再使用Sanger测序验证并行孕早期产前诊断,可有效预防X-SCID患儿出生。Objective To explore the feasibility of exome sequencing combined with Sanger sequencing applied to pedigree analysis and prenatal diagnosis of X-linked severe combined immunodeficiency(X-SCID). Methods The medical history and family history of an X-SCID propositus were analyzed retrospectively.Exome sequencing technique was used to sequence the exome of immune deficiency-related genes in the propositus,then the DNA was extracted from the peripheral blood of the propositus′s parents and the validation was conducted by Sanger sequencing technique after pathogenic gene trap.The pathogenic gene of the propositus was confirmed to be inherited from his mother,then the DNA was extracted from the villus tissues of his mother at 9 gestational weeks and the prenatal diagnosis was performed using Sanger sequencing. Results The exome sequencing results showed that missense mutation (c.713G>A,p.Ser238Asn) existed in the interleukin 2 receptor common gamma chain(IL2RG) gene located at X chromosome of the propositus.Sanger sequencing results confirmed that heterozygous mutation existed in the same locus of the propositus′s mother and the locus of his father was normal.Missense mutation was also observed in the IL2RG gene located at X chromosome of the placental villus tissues of the propositus′s mother during repregnancy,and the fetus was diagnosed as X-SCID. Conclusion Pathogenic gene trap of X-SCID related pathogenic gene using exome sequencing ,followed by prenatal diagnosis at early pregnancy using Sanger sequencing for verification,can effectively prevent the birth of X-SCID infants.

关 键 词：X-连锁重症联合免疫缺陷 白细胞介素2受体的γ共用链 外显子测序 Sanger测序 家系分析 产前诊断 病例报告 

分 类 号：R714[医药卫生—妇产科学]