A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome.
Clin Immunol
; 148(2): 279-86, 2013 Aug.
Article
en En
| MEDLINE
| ID: mdl-23803409
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.
Palabras clave
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
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Citidina Desaminasa
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Síndrome de Inmunodeficiencia con Hiper-IgM
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Mutación
Límite:
Adolescent
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Child
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Female
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Humans
País/Región como asunto:
America do sul
/
Brasil
Idioma:
En
Año:
2013
Tipo del documento:
Article