Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome

Recent studies have shown that mutations in a newly described RNA editing e nzyme, activation-induced cytidine deaminase (ALD), can cause an autosomal recessive form of hyper IgM syndrome. To determine the relative frequency o f mutations in AID, we evaluated a group of 27 patients with hyper IgM synd rome who did not have defects in CD40 ligand and 23 patients with common va riable immunodeficiency. Three different mutations in AID were identified i n 18 patients with hyper IgM syndrome, including 14 French Canadians, 2 Lum bee Indians, and a brother and sister from Okinawa, No mutations were found in the remaining 32 patients. In the group of patients with hyper IgM synd rome, the patients with mutations in AID were older at the age of diagnosis , were more likely to have positive isohemagglutinins, and were less Likely to have anemia, neutropenia, or thrombocytopenia. Lymphoid hyperplasia was seen in patients with hyper IgM syndrome and normal AID as well as the pat ients with hyper IgM syndrome and defects in AID. (C) 2000 Academic Press.