TY - JOUR
T1 - The polymorphism p.G219R of CD40L does not cause immunological alterations in vivo: Conclusions from a X-linked hyper IgM syndrome kindred
AU - Martinez-Martinez, Laura
AU - Gonzalez-Santesteban, Cecilia
AU - Badell, Isabel
AU - de la Calle-Martin, Oscar
PY - 2012/10/1
Y1 - 2012/10/1
N2 - Hyper-IgM syndromes (HIGM) are characterized by low levels of IgG, IgA and IgE and normal to high levels of IgM. Patients with these syndromes present recurrent infections due to an impaired immunoglobulin maturation. The most prevalent form of HIGM, X-linked hyper IgM syndrome (XHIM), is caused by mutations in the gene encoding the CD40 ligand (CD40LG). We present two siblings with XHIM caused by a large CD40LG deletion affecting more than half of the gene, and extended from the end of intron 3 to far upstream of the promoter regions. Genetic analysis in the maternal family discovered the CD40LG219R polymorphism in several members. Segregation of this polymorphism in the kindred indicated that the deletion of CD40LG was a de novo mutation in the mother. Although half of her CD4+ T cells did not express CD40L and the other half expressed the CD40LG219R variant, the mother was healthy. This suggests that this polymorphism is not pathogenic by itself although it has been recently related to X-linked lymphoproliferative syndrome. © 2012 Elsevier Ltd.
AB - Hyper-IgM syndromes (HIGM) are characterized by low levels of IgG, IgA and IgE and normal to high levels of IgM. Patients with these syndromes present recurrent infections due to an impaired immunoglobulin maturation. The most prevalent form of HIGM, X-linked hyper IgM syndrome (XHIM), is caused by mutations in the gene encoding the CD40 ligand (CD40LG). We present two siblings with XHIM caused by a large CD40LG deletion affecting more than half of the gene, and extended from the end of intron 3 to far upstream of the promoter regions. Genetic analysis in the maternal family discovered the CD40LG219R polymorphism in several members. Segregation of this polymorphism in the kindred indicated that the deletion of CD40LG was a de novo mutation in the mother. Although half of her CD4+ T cells did not express CD40L and the other half expressed the CD40LG219R variant, the mother was healthy. This suggests that this polymorphism is not pathogenic by itself although it has been recently related to X-linked lymphoproliferative syndrome. © 2012 Elsevier Ltd.
KW - CD40LG gene
KW - Haematopoietic stem cell transplantation
KW - Non-pathological polymorphisms
KW - X-linked hyper-IgM syndrome
U2 - 10.1016/j.molimm.2012.06.002
DO - 10.1016/j.molimm.2012.06.002
M3 - Article
VL - 52
SP - 237
EP - 241
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 3-4
ER -