Activation-induced cytidine deaminase (AID) is a DNA editing protein that plays an essential role in three major events of immunoglobulin (Ig) diversification: somatic hypermutation, class switch recombination and Ig gene conversion. Mutations in the AID gene (AICDA) have been found in patients with autosomal recessive Hyper-IgM (HIGM) syndrome type 2. Here, two 9- and 14-year-old Brazilian sisters, from a consanguineous family, were diagnosed with HIGM2 syndrome. Sequencing analysis of the exons from AICDA revealed that both patients are homozygous for a single C to G transversion in the third position of codon 15, which replaces a conserved Phenylalanine with a Leucine. To our knowledge, this is a new AICDA mutation found in HIGM2 patients. Functional studies confirm that the homologous murine mutation leads to a dysfunctional protein with diminished intrinsic cytidine deaminase activity and is unable to rescue CSR when introduced in Aicda(-/-)stimulated murine B cells. We briefly discuss the relevance of AICDA mutations found in patients for the biology of this molecule.
Keywords: AID; APOBEC1; Activation-induced cytidine deaminase; CSR; GC; Hyper-immunoglobulin M; Mutation; NES; NLS; PI; SHM; activation-induced cytidine deaminase; apolipoprotein B mRNA editing catalytic polypeptide 1; class switch recombination; gene conversion; hAID; human AID; nuclear export signal; nuclear localization signal; propidium iodide; somatic hypermutation; wild type; wt.
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