一例IKBKG基因新突变导致外胚层发育不良伴免疫缺陷临床特征分析  

A Case Report of Clinical Features Analysis of a Novel IKBKG Variant Leading to Anhidrotic Ectodermal Dysplasia and Immunodeficiency

作　　者：黄晓梅 罗颖[1] 何庭艳[1] 许永彬 夏宇[1] 杨芝 朱晓娜 黄艳艳 翁若航 杨军[1] 王琳琳 HUANG Xiaomei;LUO Ying;HE Tingyan;XU Yongbin;XIA Yu;YANG Zhi;ZHU Xiaona;HUANG Yanyan;WENG Ruohang;YANG Jun;WANG Linlin(Department of Rheumatology and Immunology,Shenzhen Children′s Hospital,Shenzhen 518038,China)

机构地区：[1]深圳市儿童医院风湿免疫科,深圳518038

出　　处：《罕见病研究》2024年第4期492-500,共9页Journal of Rare Diseases

基　　金：国家重点研发计划(2021YFC2702001)。

摘　　要：IKBKG是核因子κB(NF-κB)信号通路的关键调节分子,其编码基因发生突变,可导致外胚层发育不良伴免疫缺陷(EDA-ID)。本文报道1例男性患儿,其存在前额稍凸出、毛发稀疏、皮肤色素沉着、圆锥牙等外胚层发育不良表现,生后1月出现反复感染,病原体覆盖细菌、真菌、病毒,并伴有低丙种球蛋白血症,符合EDA-ID的表型。基因分析显示患儿IKBKG基因10号外显子存在一个新的半合子变异c.1249T>G(p.Cys417Gly),其母为该突变携带者。免疫评估提示患儿记忆性B淋巴细胞显著减少,T细胞受体Vβ多样性无明显受限,T细胞在植物凝集素刺激下增殖功能受损,Th细胞分泌干扰素-γ显著减少,IκBα降解率无明显下降。本文通过总结该患儿临床特征并进行功能验证,以期提高临床医生对该疾病的认识。对于早期发病、表现为反复感染伴外胚层发育不良的男性患儿,需考虑IKBKG基因突变。基因分析需排除假基因的干扰,对于新突变需进行免疫评估及功能验证。IKBKG is the essential modulator for nuclear factor-κB(NF-κB)signaling pathway,and mutations within this gene can lead to anhidrotic ectodermal dysplasia and immunodeficiency(EDA-ID).Here we report a male patient,who presented with mild frontal bossing,sparse hair,skin pigmentation,conical teeth,and recurrent infections involving bacteria,fungi,and viruses after one month of age,together with hypogammaglobu-linemia.These symptoms were consistent with the phenotype of EDA-ID.Genetic analysis revealed a hemizygous mutation c.1249T>G(p.Cys417Gly)in exon 10 of the IKBKG gene in the patient.The mother of the patient was identified as heterozygous carriers of the same mutation.Immunological assessment revealed a significant reduction in memory B cells.The patient showed no skewed TCR diversity.PHA-induced T-cell proliferation was impaired.IFN-γsecretion by Th cells was significantly reduced after PHA stimulation.IκBαdegradation rate retained the same in the patient.We summarized the clinical features of the patient and conducted immunological analysis,in order to increase pediatricians′awareness of this rare disease.For boys with early-onset recurrent infections together with ectodermal dysplasia,IKBKG mutation should be considered.In addition,genetic analysis is needed to exclude pseudogene interference and functional evaluations are required.

关 键 词：IKBKG基因 假基因 外胚层发育不良 免疫缺陷 

分 类 号：R725.9[医药卫生—儿科]