Five unrelated children are described with a rare autoimmune lymphoproliferative syndrome (ALPS) characterized by massive nonmalignant lymphadenopathy, autoimmune phenomena, and expanded populations of TCR-CD3+ CD4-CD8- lymphocytes. These findings, suggesting a genetic defect in the ability of T lymphocytes to respond to normal immunoregulatory mechanisms, prompted an evaluation of lymphocyte apoptosis. Each child had defective Fas-mediated T lymphocyte apoptosis associated with a unique, deleterious Fas gene mutation. One mutation appeared to cause a simple loss of function; however, four others had a dominant negative phenotype when coaxpressed with normal Fas. Family studies demonstrated the inheritance of the mutant Fas alleles. The occurrence of Fas mutations together with abnormal T cell apoptosis in ALPS patients suggests an involvement of Fas in this recently recognized disorder of lymphocyte homeostasis and peripheral self-tolerance. © 1995.
Fisher, G. H., Rosenberg, F. J., Straus, S. E., Dale, J. K., Middelton, L. A., Lin, A. Y., … Puck, J. M. (1995). Dominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell, 81(6), 935–946. https://doi.org/10.1016/0092-8674(95)90013-6