title: The polymorphism p.G219R of CD40L does not cause immunological alterations in vivo: conclusions from a X-linked hyper IgM syndrome kindred.
abstract: 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 CD40L(G219R) 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 CD40L(G219R) 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.
authors: Immunology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, C/Pare Claret, 167. E08025 Barcelona, Spain.
authors: Laura
authors: L
authors: Martinez-Martinez
authors: Cecilia
authors: C
authors: Gonzalez-Santesteban
authors: Isabel
authors: I
authors: Badell
authors: Oscar
authors: O
authors: de la Calle-Martin
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology*; D002675:Child, Preschool; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000235:genetics* / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood*; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D023201:CD40 Ligand; D007073:Immunoglobulin E