Mutational screening of the CD40 ligand (CD40L) gene in patients with X linked hyper-IgM syndrome (XHIM) and determination of carrier status in female relatives.

AIMS To analyse the gene encoding the CD40 ligand (CD40L) in 11 Australian patients from 10 unrelated families with the X linked hyper-IgM (XHIM) phenotype. METHODS The CD40L gene was screened for mutations using direct sequencing of exon specific polymerase chain reaction (PCR) products. RESULTS Ten mutations were identified. Seven of these mutations have been described previously, whereas three new nonsense mutations were identified, namely: E108X (c.322G>T), G167X (c.499G>T), and C218X (c.654C>A). Ten of 15 female family members revealed both a mutated allele and a normal allele, indicating that they were XHIM carriers. CONCLUSION The 10 mutations (including the three new ones) identified in this study reflect the heterogeneity of the CD40L gene, and indicate the need for accurate and reliable molecular testing of those patients suspected of XHIM.