NEMO基因新突变致少汗型外胚层发育不良伴免疫缺陷病1例

Novel missense mutation of NEMO gene in a boy with ectodermal dysplasia and immunodeficiency

目的探讨1例少汗型外胚层发育不良伴免疫缺陷(ectodermal dysplasia and immunodeficiency,EDA-ID)患儿的临床特征和基因突变。方法患儿于2014年12月收入我院肾脏免疫科,根据其临床表现及家族史,常规免疫学筛查除外常见原发性免疫缺陷病(primary immunodeficiency disease,PID),qRT-PCR在mRNA水平检测患儿与对照(患儿父亲)IL-12/IFN-γ通路的完整性,并对患儿及其家系的NEMO基因进行分析。结果患儿反复发热,皮肤苍白干燥,头发稀疏,前额轻微突出,无牙胚发育,有真菌和卡介苗(BCG)感染。全血经BCG与IFN-γ联合刺激后,与单独的BCG刺激比较,患儿IL-12B的mRNA表达降低(P<0.05),而健康对照组IL-12B表达明显增加。患儿NEMO基因第10外显子出现一个纯合错义突变位点c.1241T>A,p.V414D,其母亲与二姨为相同位点的杂合突变。结论反复发热伴BCG感染的男性患儿合并皮肤苍白无汗、毛发稀疏、无牙等外胚层发育不良表型时,应考虑NEMO基因突变,母系家族色素失禁的病史有助于诊断,结合IL-12/IFN-γ轴的功能完整性检测和基因分析,可以早期诊断EDA-ID。

Objective To explore the clinical features and NEMO gene mutation in a boy with ectodermal dysplasia and immunodeficiency （EDA-ID）. Methods According to the patient＇ s clinical presentation and family history, the integrity of the IL-12/IFN-γ axis was detected by Q-RT-PCR after ruling out the common primary immunodeficiency disease （PID） , and then NEMO gene was sequenced. Results The patient showed recurrent fever, pale skin, sparse hair, mild frontal bossing, and fungus and BCG infections. The X-ray of the head revealed no obvious tooth germ. The expression of IL-12B mRNA in the whole blood cells was reduced more after stimulation with BCG plus IFN--/ than BCG alone （ P 〈 0.05 ）. NEMO gene sequencing analysis found 1241T 〉 A substitution mutation in exon 10, predicting valine-to- aspartic acid missense mutation at the 414th amino acid site （p. V414D）. The mother and one of her sisters had heterozygous mutations at the same site. Conclusion Male children with BCG infections and recurrent fever should be considered to have mutation of NEMO gene, especially when there are some ectodermal dysplasia phenotypes such as pale and dry skin without sweat, sparse hair and no teeth. Matrilineal family history of incontinentia pigmenti is helpful to diagnosis. EDA-ID can be diagnosed early by combining the integrity test of IL-12/IFN-γ axis and genetic analysis.