title: Hyper-immunoglobulin M syndrome caused by a mutation in the promotor for CD40L.
abstract: Hyper-immunoglobulin M (IgM) syndrome (HIGM) is a rare primary immunodeficiency characterized by elevated or normal IgM and absent or markedly decreased amounts of IgG, IgA and IgE. The X-linked form (HIGM1) is the most common type and is caused by mutations in the gene for CD40L, a T-cell surface molecule required for T-cell driven immunoglobulin class switching by B cells. In the present study we have identified a patient with X-linked hyper-IgM who failed to express CD40L on the cell surface of CD4(+) T lymphocytes. Sequence analysis of CD40L genomic DNA showed no mutations. CD40L mRNA was absent and sequence analysis of the CD40L promotor revealed a mutation at position -123 from the transcription start site. The mutation in the promotor region likely contributed to the decreased transcription as demonstrated by a luciferase reporter assay.
authors.affiliation: Laboratory Medicine, Immunology, University Hospital Leuven, Belgium.
authors.forename: Erna
authors.initials: E
authors.lastname: Van Hoeyveld
authors.forename: Ping-Xia
authors.initials: PX
authors.lastname: Zhang
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
authors.forename: Ramsay
authors.initials: R
authors.lastname: Fuleihan
authors.forename: Xavier
authors.initials: X
authors.lastname: Bossuyt
mesh_terms: D023201:CD40 Ligand / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics*; D007075:Immunoglobulin M / Q000097:blood*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007223:Infant; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013577:Syndrome
chemical_list: D007075:Immunoglobulin M; D023201:CD40 Ligand