Mutations in Fas Associated with Human Lymphoproliferative Syndrome and Autoimmunity

TLDR

Fas (Apo1/CD95) is a cell surface receptor that mediates apoptotic cell death. The authors examined Fas expression and function in three children with lymphoproliferative syndrome, including two siblings, some of whom also had autoimmune disorders. A large deletion in the Fas gene causing loss of surface expression was found in the most affected patient, while the siblings exhibited a milder intracytoplasmic domain deletion and impaired apoptosis, underscoring Fas’s essential regulatory role and its potential link to human autoimmune disease.

Abstract

Fas (also known as Apo1 and CD95) is a cell surface receptor involved in apoptotic cell death. Fas expression and function were analyzed in three children (including two siblings) with a lymphoproliferative syndrome, two of whom also had autoimmune disorders. A large deletion in the gene encoding Fas and no detectable cell surface expression characterized the most affected patient. Clinical manifestations in the two related patients were less severe: Fas-mediated apoptosis was impaired and a deletion within the intracytoplasmic domain was detected. These findings illustrate the crucial regulatory role of Fas and may provide a molecular basis for some autoimmune diseases in humans.