JAK3突变致严重联合免疫缺陷 1例报告并文献复习

目的    报道我国首例JAK3突变致严重联合免疫缺陷（SCID）患儿资料并文献复习。方法    2011-04-25重庆医科大学附属儿童医院对1例疑似SCID 患儿血标本（患儿、患儿父母及外祖母）进行JAK3基因PCR扩增、基因测序、单核苷酸多态性（SNPs）及TCR Vβ亚家族克隆多态性分析。结果    患儿免疫表型符合T-B+NK-，主要表现为反复呼吸道、消化道感染。JAK3基因突变为复合杂合突变，两个等位基因均为错义突变，分别来自父系第9外显子（1308G＞A：R403H）和母系的第24外显子（3354G＞A：R1085Q），患儿父母和外祖母分别为上述突变携带者。患儿T细胞抗原受体库未能检出。查阅文献截止2007年，国内外共35例患儿30种JAK3基因突变在JAK3 base注册，免疫学表型均符合T-B+NK- SCID，但临床表现从经典SCID到基本正常均有报道。结论    JAK3缺陷患者外周血T细胞及NK细胞严重减少，B细胞数量正常或稍减少但存在功能障碍，免疫球蛋白水平明显降低，故临床表现为反复细菌和病毒感染，对临床症状及实验室检查高度怀疑JAK3缺陷的患者，可通过STAT5磷酸化分析、基因测序、蛋白印迹或流式测定JAK3蛋白含量等技术进一步明确诊断。主要治疗方式为干细胞移植，若不及时进行免疫重建多数死于婴儿期。

One case of severe combined immunodeficiency caused by JAK3 mutation and literature Review.

Objective    To report the first JAK3 deficiency patient in China and to have literature review. Methods    On April 25，2011，the blood samples of 1 case of suspected SCID  child，his parents and grandparents were detected with PCR amplification and sequencing of JAK3 gene， single nucleotide polymorphism（SNPs） and TCRVβ analysis in Children’s Hospital of Chongqing Medical University. Results    The mutation of this patient was a compound heterozygous mutation，both alleles being missense mutations. One allele （1308G＞A：R403H） was located in the eighth exon of JAK3，which came from her father， the other （3354G＞A：R1085Q） located in the twenty-third exon of JAK3，which came from her mother.Her parents and grandmother were carries.We confirmed these mutations were disease-caused mutations not SNPs by sequencing the 9th and 24th exon of JAK3 gene of twenty common people. Unfortunately，we failed to detect The TCRVβ of this patient because of the limited number of circulating T cells. Up to 2007，thirty mutations and thirty-five patients had been registered for JAK3 deficiency in JAK3base. Their immunophenotype was uniformly T-B+NK-SCID，but the clinical phenotype of them varied from classical SCID to almost normal immune function. Conclusion    JAK3 deficiency is a rare autosomal recessive severe combined immunodeficiency disease （SCID），characterized by recurrent bacteria and virus infection，absence of T and NK cells but normal number of poorly functioning B cells in the peripheral blood. The diagnosis depends on stat5 phosphorylation,sequencing of JAK3 gene and detect the JAK3 protein by western blot or flow cytometry, when JAK3 deficiency is suspected. The most effective treatment for JAK3 deficiency is hematopoietic stem cell transplantation （HSCT），and patients who don’t receive HSCT will usually die in infancy.