拷贝数变异致高IgM综合征1例并文献复习

目的:探讨拷贝数变异致高IgM综合征的临床特征、免疫学特点及基因测序情况。方法:对1例拷贝数变异致高IgM综合征患儿的临床、实验室及遗传资料进行分析,并检索拷贝数变异所致高IgM综合征的相关文献。结果:患儿男,生后反复感染,伴黄疸及门静脉海绵样变性,血IgG及IgA下降,血中性粒细胞减少。父母非近亲结婚,无阳性家族史。高通量测序常规生物信息分析未发现致病突变,拷贝数变异分析示CD40LG基因大片段缺失,DNA样本CD40LG基因1-5号外显子PCR无扩增,cDNA扩增无产物。流式细胞术检测淋巴细胞CD40L蛋白表达缺如。文献检索结果显示,高IgM综合征以点突变最为多见,CD40LG、AICDA基因存在拷贝数变异报道。结论:拷贝数变异与点突变所致的高IgM综合征临床表现、免疫学指标无明显差异。对临床可疑高IgM综合征但二代测序未发现致病突变的病例需进行拷贝数变异分析。

Hyper-IgM syndrome caused by copy number variation:One case report and literature review

Objective To investigate the clinical,immunological and genetic characteristics of hyper-IgM syndrome(HIgM)caused by copy number variation.Methods We collated the data of a child with HIgM syndrome caused by copy number variation of CD40LG and searched the literature at the same time.Results The patient had recurrent infection and opportunistic infection along with diarrhea,jaundice and portal vein cavernous degeneration. There was no positive family history. Next generation sequencing bioinformatics analysis revealed no pathogenic mutation but copy number variation showed a large deletion of CD40LG gene and PCR also showed no amplification of the cDNA.The level of IgG and IgA decreased and the blood routine test showed neutropenia.The expression of CD40L by flow cytometry was negative and the number of memory B cells and plasma cells reduced. CD40LG gene mutation is the most common pathogenic gene of HIgM syndrome, as well as copy number variation analysis,followed by AICDA gene.Conclusion For children with highly suspected XHIgM,but no suspicious CD40LG pathogenic mutation, it is necessary to consider copy number variation,especially that caused by CD40LG and AICDA gene.