CAJ | 학술논문

目的对2个X-连锁重症联合免疫缺陷病(X-SCID)家系进行致病基因突变分析及产前诊断.方法收集2012年1月至2013年2月郑州大学第一附属医院就诊的2个X-SCID家系中患者及其家庭成员的外周血,提取基因组DNA,应用PCR扩增和直接测序方法对2个X-SCID家系成员进行白细胞介素2受体基因IL2RG基因测序,分析IL2RG基因外显子区和剪切区DNA序列改变情况,同时选择100名健康对照个体进行IL2RG基因序列分析.在确定每个家系基因型后,对家系1中的高危胎儿抽取绒毛进行产前诊断.对家系1中可疑女性进行携带者检测.结果 2个X-SCID家系分别发现1种IL2RG基因新突变.家系1中,患者及其母亲携带IL2RG基因c.361-363delGAG(p.E121del)突变;家系2中,先证者母亲携带IL2RG基因c.510-511insGAACT(p.W173X)杂合突变.c.361-363delGAG(p.E121del)和c.510-511 insGAACT(p.W173X)突变均为新发现的突变,100名健康个体X-SCID基因相应区域测序,未发现有上述同样序列改变.对明确致病突变的家系1中胎儿行孕早期产前诊断,胎儿为女性,未携带致病突变,家系1夫妇选择继续妊娠,胎儿娩出后随访结果与产前诊断结果一致.对家系1中可疑女性Ⅱ-3行携带者检测,证实为非携带者.结论发现2个IL2RG基因新变异,IL2RG基因p.E121del和p.W173X突变是家系1和家系2患者的致病原因;有X-SCID生育史的夫妇再次生育时,应用基因测序技术行产前IL2RG基因突变分析可以有效地预防患儿出生,并且可进行可疑女性的携带者检测.
목적 대2개X-련쇄중증연합면역결함병(X-SCID)가계진행치병기인돌변분석급산전진단.방법 수집2012년1월지2013년2월정주대학제일부속의원취진적2개X-SCID가계중환자급기가정성원적외주혈,제취기인조DNA,응용PCR확증화직접측서방법대2개X-SCID가계성원진행백세포개소2수체기인IL2RG기인측서,분석IL2RG기인외현자구화전절구DNA서렬개변정황,동시선택100명건강대조개체진행IL2RG기인서렬분석.재학정매개가계기인형후,대가계1중적고위태인추취융모진행산전진단.대가계1중가의녀성진행휴대자검측.결과 2개X-SCID가계분별발현1충IL2RG기인신돌변.가계1중,환자급기모친휴대IL2RG기인c.361-363delGAG(p.E121del)돌변;가계2중,선증자모친휴대IL2RG기인c.510-511insGAACT(p.W173X)잡합돌변.c.361-363delGAG(p.E121del)화c.510-511 insGAACT(p.W173X)돌변균위신발현적돌변,100명건강개체X-SCID기인상응구역측서,미발현유상술동양서렬개변.대명학치병돌변적가계1중태인행잉조기산전진단,태인위녀성,미휴대치병돌변,가계1부부선택계속임신,태인면출후수방결과여산전진단결과일치.대가계1중가의녀성Ⅱ-3행휴대자검측,증실위비휴대자.결론 발현2개IL2RG기인신변이,IL2RG기인p.E121del화p.W173X돌변시가계1화가계2환자적치병원인;유X-SCID생육사적부부재차생육시,응용기인측서기술행산전IL2RG기인돌변분석가이유효지예방환인출생,병차가진행가의녀성적휴대자검측.
Objective To evaluate the diagnostic feasibility of mutation analysis and prenatal genetic diagnosis genetic analysis of IL2RG gene in two 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 mother in family 1 and the parents of another deceased child with X-SCID in family 2 from January 2012 to February 2013 were collected.Eight exons comprising IL2RG open reading frame and their exon/intron boundaries were analyzed by bi-directional direct sequencing of polymerase chain reaction (PCR) products.Prenatal genetic diagnoses were performed by chorionic villus sampling after the genotypes of maternal probands were identified in family 1.Results Two mutations of IL2RG gene were identified in these two families.The c.361-363delGAG (p.E121del) mutation was identified in family 1.The c.510-511insGAACT (p.W173X) mutation appeared in family 2.The two mutations of c.361-363delGAG (p.E121del) and c.510-511insGAACT (p.W173X) were novel.The two novel mutations were absent in 100 normal controls.The pregnancy in family 1 continued and the infant showed no symptom of X-SCID at 1 year after birth.The aunt (Ⅱ-3) of proband in family 1 was not a carrier.The female fetus in family 1 had no mutation.Conclusions Two novel mutations of c.361-363delGAG(p.E121del) and c.510-511insGAACT (p.W173X) in IL2RG gene may be a major cause of disease in two families with X-SCID.And direct sequencing of IL2RG gene provides genetic counseling,prenatal diagnosis and carrier screening for families with X-SCID.