Molecular pathology of the X-linked hyper-immunoglobulin M syndrome: Detection of wild-type transcripts in a patient with a complex splicing defect of the CD40 ligand
| Autor: | John K. French, R. Prestidge, W Fanslow, Rohan Ameratunga, J McKee, J. Marbrook |
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| Předmět: |
Male
Microbiology (medical) X Chromosome Adolescent Transcription Genetic CD40 Ligand Molecular Sequence Data Clinical Biochemistry Immunology Ligands Polymerase Chain Reaction Immunoglobulin D Antigen Hypergammaglobulinemia Humans Immunology and Allergy Interleukin 4 Membrane Glycoproteins Base Sequence biology Point mutation Wild type Exons Immunoglobulin Class Switching Molecular biology Introns Pedigree Alternative Splicing Immunoglobulin M Immunoglobulin class switching Mutation RNA splicing biology.protein Research Article |
| Zdroj: | Scopus-Elsevier |
| Popis: | The X-linked hyper-immunoglobulin M syndrome (XHIM) is a primary immune deficiency disorder characterized by an inability to produce immunoglobulin isotypes other than immunoglobulin M (IgM) and IgD. Recently, a B-cell surface antigen (CD40) and its conjugate T-cell counterstructure (CD40 ligand) were shown to mediate immunoglobulin isotype switching in the presence of cytokines such as interleukin 4. Most patients with XHIM have been shown to have mutations of the extracellular domain of the CD40 ligand. Here we describe a novel point mutation of an intronic splice acceptor site which results in a complex splicing defect of the CD40 ligand in a patient with XHIM. In addition to two species of deleted transcripts, wild-type transcripts were also detected in this individual. The demonstration of wild-type CD40 ligand transcripts may be an explanation for previous observations suggesting that some XHIM patients are able to undergo immunoglobulin isotype switching in vivo. |
| Databáze: | OpenAIRE |
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