基于高通量测序的单体型分析在地中海贫血-HLA配型的植入前遗传学诊断中的应用  

Application of NGS-based SNP haplotyping for preimplantation genetic diagnosis for beta-thalassemia and HLA matching

作　　者：阳彦[1] 刘艳秋[1] 陆清[1] 陈佳[1] 罗海艳 马鹏鹏[1] Yang Yan;Liu Yanqiu;Lu Qing;Chen Jia;Luo Haiyan;Ma Pengpeng(Prenatal Diagnosis Center of Jiangxi Women and Children’s Hospital,Nanchang,Jiangxi 330006,China)

机构地区：[1]江西省妇幼保健院产前诊断中心,南昌330006

出　　处：《中华医学遗传学杂志》2019年第11期1090-1093,共4页Chinese Journal of Medical Genetics

基　　金：江西省卫计委科技计划(20181119).

摘　　要：目的探讨基于高通量测序(next-generation sequencing,NGS)的单核苷酸多态性(singlenucleotide polymorphism,SNP)单体型分析在β地中海贫血(简称β-地贫)暨HLA配型植入前遗传学诊断(preimplantation genetic diagnosis,PGD)中的应用.方法夫妇1同为βIVS2-654变异携带者,曾生育1重型β-地贫患儿;夫妇2分别为βCD41-42与βIVS2-654变异携带者;夫妇3分别为βCD17与βIVS2-654变异携带者,曾引产1双重杂合子胎儿.应用NGS-SNP单体型分析和Sanger测序技术,为夫妇1提供β-地贫-HLA的PGD,为夫妇2、3提供β-地贫PGD.结果夫妇1获得2枚HLA配型相符且不致病的囊胚,移植1枚并成功妊娠,产前诊断的结果与PGD一致,于孕39周分娩一健康新生儿,并取脐带血进行造血干细胞移植.夫妇2获得不致病囊胚7枚,第2次移植成功妊娠,产前诊断结果与PGD一致.夫妇3获得不致病且无致病性拷贝数重复和缺失的囊胚2枚,移植1枚成功妊娠,产前诊断结果与PGD一致.结论NGS-SNP单体型分析是β-地贫HLA配型PGD的有效工具,可帮助携带β-地贫变异的夫妇获得健康的胚胎,同时为患儿的造血干细胞移植治疗提供机会.Objective To assess the value of next-generation sequencing(NGS)-based single nucleotide polymorphism(SNP)haplotyping for preimplantation genetic diagnosis(PGD)for betathalassemia coupled with human leukocyte antigen(HLA)matching.Methods Three couples were recruited.Couple 1 both carried aβIVS-2-654 variation and had previously given birth to a son withβthalassemia major.Couple 2 respectively carriedβcd4142 andβIVS-2-654 but had no history of pregnancy.Couple 3 respectively carriedβCD17andβIVS-2-654,and had a daughter carryingβCD17.Results For couple 1,NGS-SNP typing identified two embryos not only unaffected with thalassemia but also with matched HLA.One blastocyst was transferred and resulted in successful pregnancy.A healthy baby was born at 39th week of gestation.Its umbilical blood was used to treat the sick brother through hemopoietic stem cell transplantation.For couple 2,seven blastocysts were obtained.Second transplantation has resulted in successful pregnancy.Prenatal diagnosis was consistent with PGD.For couple 3,two blastocysts not only unaffected with thalassemia but also with no pathogenic copy number variations were obtained.Transfer of one blastocyte resulted in successful pregnancy,and prenatal diagnosis was consistent with PGD.Conclusion NGS-based SNP typing is an useful tool for selecting embryos unaffected with beta thalassemia and matched HLA through PGD.

关 键 词：Β-地中海贫血 植入前遗传学诊断 HLA-配型 二代测序 单体型分析 

分 类 号：R714[医药卫生—妇产科学]