Organization of the human CD40L gene: Implications for molecular defects in X chromosome-linked hyper-IgM syndrome and prenatal diagnosis

Journal Article · Tue Mar 15 04:00:00 EST 1994 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.91.6.2110· OSTI ID:86517

Villa, A; Macchi, P P; Strina, D; Frattini, A; Lucchini, F; Patrosso, C M; Vezzoni, P ^[1]; Notarangelo, L D; Giliani, S; Mantuano, E ^[2]

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1. Instituto di Technologie Biomediche Avanzate, Milan (Italy)
2. Universita di Brescia (Italy); and others

Recently, CD40L has been identified as the gene responsible for X chromosome-linked hyper-IgM syndrome (HIGM1). CD40L on activated T cells from HIGM1 patients fails to bind B-cell CD40 molecules, and subsequent analysis of CD40L transcripts by reverse transcription PCR demonstrated coding region mutations in these patients. This approach, however, is of limited use for prenatal diagnosis of HIGM1 in the early-gestation fetus. In this report, the authors have defined the genomic structure of the CD40L gene, which is composed of five exons and four intervening introns. With this information, the authors have defined at the genomic level the CD40L coding region. These different deletions arose from three distinct mechanisms, including (i) a splice donor mutation with exon skipping, (ii) a splice acceptor mutation with utilization of a cryptic splice site, and (iii) a deletion/insertion event with the creation of a new splice acceptor site. In addition, they have performed prenatal evaluation of an 11-week-old fetus at risk for HIGM1. CD40L genomic clones provide a starting point for further studies of the genetic elements that control CD40L expression. Knowledge of the CD40L gene structure will prove useful for the identification of additional mutations in HIGM1 and for performing genetic counseling about this disease. 54 refs., 4 figs., 1 tab.

• Sponsoring Organization: USDOE
• OSTI ID: 86517
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 6 Vol. 91; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANTIGENS
DNA SEQUENCING
GENE MUTATIONS
HUMAN X CHROMOSOME
IMMUNOGLOBULINS
METABOLIC DISEASES