title: Structural organization of the gene for CD40 ligand: molecular analysis for diagnosis of X-linked hyper-IgM syndrome.
abstract: CD40 ligand (CD40L) on activated T cells plays a crucial role for Ig heavy-chain class switching and the mutation of the gene for this ligand in the X-chromosome causes immunodeficiency with hyper-IgM (X-HIM). We isolated and characterized the human genomic clone for CD40 L to obtain information about the transcriptional regulatory regions of the gene and to develop a molecular diagnostic method for X-HIM patients. The genomic DNA isolated was over 12 kb long containing 5 exons that cover full sequence of mRNA for the ligand. DNA motif analysis based on transcription factor database revealed the presence of a GATA 1 box at around -265 bp. The typical TATA box, CAT site or GC rich region was not found in the 5' flanking region. However, two possible TATA like sequences were found at around -27 and -136 bp. Using the oligonucleotide primers corresponding to the introns, we performed a PCR-SSCP analysis of each exon from a patient with X-HIM syndrome and detected abnormality in exon 5. When sequenced, dinucleotide deletion in this exon was found in the patient and in one X allele of his mother as the only different sequence from that of the control gene. This procedure is simple and could be used for diagnosis of the X-HIM syndrome.
authors.affiliation: Department of Genetics, Mitsubishi Yuka Bio-Clinical Laboratories, Inc., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shimadzu
authors.forename: H
authors.initials: H
authors.lastname: Nunoi
authors.forename: H
authors.initials: H
authors.lastname: Terasaki
authors.forename: R
authors.initials: R
authors.lastname: Ninomiya
authors.forename: M
authors.initials: M
authors.lastname: Iwata
authors.forename: S
authors.initials: S
authors.lastname: Kanegasaka
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D023201:CD40 Ligand; D004247:DNA; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D006942:Hypergammaglobulinemia / Q000175:diagnosis / Q000235:genetics*; D007075:Immunoglobulin M; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D014960:X Chromosome
chemical_list: D007075:Immunoglobulin M; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D004247:DNA