A SINGLE-STRAND CONFORMATION POLYMORPHISM STUDY OF CD40 LIGAND - EFFICIENT MUTATION ANALYSIS AND CARRIER DETECTION FOR X-LINKED HYPER IGM SYNDROME

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