摘要
目的探讨DOCK 8基因变异导致的反复感染型高IgE综合征的临床及遗传特征。方法回顾分析2例高IgE综合征患儿的临床资料,包括高通量测序分析,致病位点Sanger验证,以及外周血DOCK 8基因表达水平。结果男女患儿各1例,分别为5岁2个月和4岁8个月。2例患儿均因反复感染、持续皮疹或脓疱等就诊。患儿无特殊面容,血清IgE水平显著升高,外周血中嗜酸性粒细胞水平明显上升。全外显子测序分析发现女性患儿的DOCK 8基因存在IVS2+1G>A和c.1729G>A(p.A 577T)复合杂合变异,分别来自其父母。男性患儿的DOCK 8基因存在父源c.2248G>A(p.E 750K)和母源c.1685T>G(p.L 562R)复合杂合变异。生物信息学分析发现p.A 577T、p.E 750K以及p.L 562R三个错义变异在不同的物种之间保守。实时荧光定量PCR结果显示女性患儿外周血中DOCK 8基因表达水平显著降低。结论DOCK 8基因变异是感染型高IgE综合征的常见病因,扩大了DOCK 8基因变异谱。
Objective To explore the clinical and genetic features of hyper-IgE syndrome with recurrent infection caused by DOCK8 gene variation.Methods The clinical data of hyper-IgE syndrome in 2 children were analyzed retrospectively,including whole exome sequencing,Sanger verification of pathogenic site,and the expression level of DOCK8 gene in peripheral blood.Results Both children,1 boy and 1 girl aged 5 years 2 months and 4 years 8 months respectively,were visited for recurrent infection,persistent rash or pustules.The children had no special facial features.The serum IgE level was significantly increased,and the eosinophils in peripheral blood were significantly increased.There were compound heterozygous variants of IVS2+1G>A and c.1729G>A(p.A577T)in DOCK8 gene of the girl,which came from her parents respectively.The DOCK8 gene of the boy had compound heterozygous variation of paternal C.2248G>A(p.E750K)and maternal C.1685T>G(p.L562R).Bioinformatics analysis showed that the three missense variants of p.A577T,p.E750K and p.L562R were conserved among different species.The results of real-time PCR showed that the expression level of DOCK 8 gene in peripheral blood of the girl decreased significantly.Conclusion DOCK 8 gene variation is a common cause of hyper-IgE syndrome with recurrent infection,which expands the DOCK8 gene variation spectrum.
作者
任丽颖
刘海超
郭旗
REN Liying;LIU Haichao;GUO Qi(Shanxian Central Hospital,Heze 274300,Shandong,China)
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2021年第10期779-781,共3页
Journal of Clinical Pediatrics
