TY - JOUR
T1 - A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome
AU - Caratão, Nadine
AU - Cortesão, Catarina S.
AU - Reis, Pedro H.
AU - Freitas, Raquel F.
AU - Jacob, Cristina M.A.
AU - Pastorino, Antonio C.
AU - Carneiro-Sampaio, Magda
AU - Barreto, Vasco M.
N1 - Funding Information:
We thank Maria João Amorim and Carlos Takodoro for their help and Kevin McBride for the reagents. The work from the group of M. Carneiro-Sampaio was funded by grant FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) 2008/58238-4 . The group of VM Barreto was funded by grants Marie Curie IRG ( PIRG03-GA-2008-230967 ), Associação Portuguesa Contra a Leucemia and Terry Fox Foundation (Liga Portuguesa Contra o Cancro) .
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Activation-induced cytidine deaminase
KW - Hyper-immunoglobulin M
KW - Mutation
UR - https://www.scopus.com/pages/publications/84880272979
U2 - 10.1016/j.clim.2013.05.017
DO - 10.1016/j.clim.2013.05.017
M3 - Article
C2 - 23803409
AN - SCOPUS:84880272979
SN - 1521-6616
VL - 148
SP - 279
EP - 286
JO - Clinical Immunology
JF - Clinical Immunology
IS - 2
ER -