A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome

Nadine Caratão, Catarina S. Cortesão, Pedro H. Reis, Raquel F. Freitas, Cristina M.A. Jacob, Antonio C. Pastorino, Magda Carneiro-Sampaio, Vasco M. Barreto
2013 Clinical Immunology  
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
more » ... nalysis 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.
doi:10.1016/j.clim.2013.05.017 pmid:23803409 fatcat:7bltxcy3mncopcerqcwwwgsj4u