Studies on in vitro mutagenized AID as well as its mutations in human patients with hyper-IgM (HIGM)-syndrome type II revealed that C-terminal AID mutations were defective in CSR whereas their DNA cleavage and SHM activities remained intact.
The description of the hyper-IgM condition due to mutations in the gene encoding uracil-N glycosylase has been essential for defining the DNA-editing activity of activation-induced cytidine deaminase.
The hyper immunoglobulin M (IgM) syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, and defective class switch recombination and somatic hypermutation, is a heterogenous disorder with at least 5 distinct molecular defects, including mutations of the genes coding for the CD40 ligand (CD40L) and IKK-gamma (NEMO) genes, both X-linked; and mutations of CD40, activation-induced cytidine deaminase (AICDA), and uracil-DNA glycosylase (UNG), associated with autosomal recessive HIGM syndromes.
Mutations of the Activation-Induced Cytidine Deaminase (AID) gene have been found in patients with autosomal recessive hyper-IgM (HIGM) syndrome type 2.