Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity.
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.
Rieux-Laucat
F
F
Institut National de la Santé et de la Recherche Médicale (INSERM) U 429, Hôpital Necker-Enfants Malades, Paris, France.
Le Deist
F
F
Hivroz
C
C
Roberts
I A
IA
Debatin
K M
KM
Fischer
A
A
de Villartay
J P
JP
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D002648:Child; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D019014:fas Receptor
D000954:Antigens, Surface; D019014:fas Receptor