摘要目的 确定患儿已故的疑为X-连锁严重联合免疫缺陷病1家系成员IL2RG基因突变类型,探索采用DNA测序进行产前诊断的可行性.方法 采集已故患儿的父母外周血标本及妊娠11周时的胎儿绒毛标本,常规提取基因组DNA,用聚合酶链反应扩增产物,采用双向直接测序方法,检测IL2RG基因8个外显子编码区及旁侧非编码区序列突变.结果 已故患儿母亲携带IL2RG基因c.690C＞ T(R226C)杂合突变,再次妊娠时行产前诊断确定为男性胎儿,未携带该突变;第三次妊娠又行产前诊断,确定妊娠一女性胎儿,且为杂合突变携带者,2名胎儿出生后1年随访结果与产前诊断结果一致.结论 IL2 RG基因c.690C＞ T(R226C)突变为该家系的致病突变.测序分析结合性别鉴定可对患者已故的X-连锁严重联合免疫缺陷病家系行有效的携带者筛查及产前诊断.

abstractsObjective To analyze the mutation of IL2RG gene in a Chinese family with a birth history of a dead child suspected of X-linked severe combined immunodeficiency (X-SCID),and to perform prenatal diagnosis with DNA sequencing.Method Blood samples of the parents of the dead child and chorionic villi at gestational age 11 weeks were collected.Eight exons comprising the open reading frame as well as their exon/intron boundaries of IL2RG gene were analyzed by PCR and bi-directional sequencing.Result A heterozygous nucleotide substitution c.690C ＞ T (R226C) in exon 5 was detected in the mother,but not in the father.In the second pregnancy of the mother,the mutation of R226C was not detected in the male fetus by prenatal diagnosis,and the heterozygous mutation was detected in the female fetus of the third pregnancy.The reliability of the prenatal genetic diagnosis was confirmed by the one-year follow-up after the neonates were born.Conclusion The mutation of c.690C ＞ T in IL2RG gene may be the pathologic cause of the proband with X-SCID.DNA sequencing combining sex determination is a valid strategy for prenatal diagnosis of X-SCID.