This project represents an extension of a long-standing series of collaborative studies performed to better characterize and understand immune deficiency. Mutations involving the genes for the common gamma chain (X-SCID) and Fas (ALPS) are being evaluated using direct gene sequencing with fluorescent probes. These studies have continued to identify a number of new mutations in both diseases and these data have been entered into the NIH NHGRI web site supporting each of these two disorders. An extensive evaluation of the gene encoding Fas (TNFRSF6) has been undertaken using control DNA samples from Caucasian and African American control subjects to determine the presence and frequency of single nucleotide polymorphisms in this gene. The data from this study has confirmed 9 SNPs and identified two new SNPs among the control DNA samples evaluated. The results are currently being evaluated and prepared for publication. In addition, mutation analysis of patients with hyper IgM syndrome directed at the genes encoding CD40 L and NEMO has provided provided insight into the variability of the clinical phenotype associated with mutations in NEMO at the level of the degree of immunodeficiency and the presence or absence of ectodermal dysplasia.
