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 published and submitted for publication. During the past year additional disorders have been added to the menu for mutation analysis including the CYBB gene coding for gp91phox that is deficient in X-linked CGD, the NEMO gene that is deficient in ectodermal dysplasia with hyper IgM syndrome and the CD40 ligand gene that is defective in X-linked hyper IgM syndrome. In addition, this project has provided valuable experience in the critical approaches to molecular diagnosis of genetic disorders. This procedure manuals and technical approaches used, are being used to assist with the NIH CLIA resource program in areas of molecular diagnostics and the project has also provided valuable teaching opportunities for fellows in training. This facility is also being linked into the Medical Genetics training program in NHGRI.
