A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome

J Clin Invest. 1996 Jan 1;97(1):196-201. doi: 10.1172/JCI118389.


Mutations in the gene for CD40 ligand are responsible for the X-linked form of hyper IgM syndrome. However, no clinical or laboratory findings that reliably distinguish X-linked disease from other forms of hyper IgM syndrome have been reported, nor are there tests available that can be used to confidently provide carrier detection. To identify efficiently mutations in the gene for CD40 ligand, eight pairs of PCR primers that could be used to screen genomic DNA by single strand conformation polymorphism (SSCP) were designed. 11 different mutations were found in DNA from all 13 patients whose activated T cells failed to bind a recombinant CD40 construct. The exact nature of four of these mutations, a deletion and three splice defects, could not be determined by cDNA sequencing. In addition, SSCP analysis permitted rapid carrier detection in two families in whom the source of the mutation was most likely a male with gonadal chimerism who passed the disorder on to some but not all of his daughters. These studies document the utility of SSCP analysis for both mutation detection and carrier detection in X-linked hyper IgM syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • CD40 Ligand
  • Child
  • Child, Preschool
  • DNA Mutational Analysis*
  • DNA Primers / genetics
  • Female
  • Genetic Carrier Screening
  • Genetic Linkage
  • Humans
  • Hypergammaglobulinemia / genetics*
  • Immunoglobulin M*
  • Infant
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins / genetics*
  • Molecular Sequence Data
  • Pedigree
  • Polymerase Chain Reaction / methods
  • Polymorphism, Single-Stranded Conformational*
  • Syndrome
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology
  • X Chromosome*


  • DNA Primers
  • Immunoglobulin M
  • Membrane Glycoproteins
  • CD40 Ligand