摘要目的 探讨基因筛查用于早期识别新生儿WAS基因相关疾病的临床应用价值.方法 2016年1月至2017年12月复旦大学附属儿科医院新生儿基因组计划纳入新生儿重症监护病房中的5 800例高危新生儿,采用高通量测序方法进行遗传病因的分析,检测到的11例携带WAS基因致病或可疑致病变异的新生儿.回顾性总结11例患儿(均为男性)临床特征,并结合基因变异特征,进行表型基因型分析.结果 11例患儿中5例为湿疹-血小板减少-免疫缺陷综合征(WAS),6例为X连锁血小板减少症(XLT).WAS患儿中2例在新生儿早期、3例在5～8周龄出现临床表现.3例XLT新生儿因其他疾病住院治疗,发现血小板减低.检测到WAS基因致病或可疑致病变异11个,其中7个为首次报道的致病或可疑致病变异,包括2个移码变异c.138delG和c.388_390del,4个剪接位点变异c.1453+ 1G＞A、c.734+ 1G＞C、c.135G＞A和c.1453+3G＞C,1个错义变异c.1118C＞T.另外4个已报道致病变异是c.777+ 1G＞A、c.107_108delTT、c.436delC和c.1509_*3delAGTG.3例患儿接受了造血干细胞移植治疗,2例治愈.结论 WAS基因相关疾病在新生儿期缺乏特征性表现,新生儿期基因筛查有助于早期识别和干预该类疾病.

abstractsObjective To explore the clinical value of genetic screening for early identification of WAS gene-related disorders in newborns.Methods This was a retrospective study.Neonatal Genome Project from Children's Hospital of Fudan University collected 5 800 high-risk newborns in the neonatal intensive care unit to study the patients' genetic causes using high-throughput sequencing from January 2016 to December 2017.Eleven newborns (all were boys) with pathogenic or likely pathogenic variants in WAS gene were enrolled.Data of clinical characteristics,gene variants and genotype-phenotype correlation were collected and summarized.Results Eleven patients included 5 cases with Wiskott-Aldrich syndrome (WAS) and 6 cases with X-linked thrombocytopenia (XLT).Two patients with WAS developed clinical manifestations in the early neonatal period,and 3 patients in 5-8 weeks after birth.Three neonates with XLT were hospitalized for other diseases in the first place.Their platelet count was found to be reduced after admission to hospital,and diagnosis was made after genetic testing.Eleven pathogenic or likely pathogenic variants in WAS gene were identified.Among them,7 were first reported in this study,including 2 frame shift variants c.138delG and c.388_390del,4 splicing variants c.1453+ 1G＞A,c.734+ 1G＞C,c.135G＞A and c.1453+3G＞C,and 1 missense variant c.1118C＞T.The other 4 reported variants were c.777+ 1G＞A,c.107_ 108delTT,c.436delC and c.1509_*3delAGTG.Conclusions The clinical features of WAS gene-related disorders in neonatal period lack specificity.Genetic screening in newborns plays an important role in the early diagnosis of diseases and provides providing evidence for the early intervention.