Abstract |
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.
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Authors | Nadine Caratão, Catarina S Cortesão, Pedro H Reis, Raquel F Freitas, Cristina M A Jacob, Antonio C Pastorino, Magda Carneiro-Sampaio, Vasco M Barreto |
Journal | Clinical immunology (Orlando, Fla.)
(Clin Immunol)
Vol. 148
Issue 2
Pg. 279-86
(Aug 2013)
ISSN: 1521-7035 [Electronic] United States |
PMID | 23803409
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- AICDA (activation-induced cytidine deaminase)
- Cytidine Deaminase
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Topics |
- Adolescent
- Amino Acid Sequence
- Amino Acid Substitution
- Brazil
(epidemiology)
- Child
- Cytidine Deaminase
(genetics, metabolism)
- Female
- Genetic Predisposition to Disease
- Humans
- Hyper-IgM Immunodeficiency Syndrome
(epidemiology, genetics, metabolism)
- Mutation
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