Abstract: 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.

Key words: AICDA, CD40LG, Copy number variation, Hyper-IgM syndrome, Immunodeficiency disease