title: Defective apoptosis due to a point mutation in the death domain of CD95 associated with autoimmune lymphoproliferative syndrome, T-cell lymphoma, and Hodgkin's disease.
abstract: Apoptosis via CD95 and its ligand is an important mechanism that prevents uncontrolled proliferation of activated lymphocytes and regulates lymphocyte homeostasis. The apoptosis receptor CD95 is a transmembrane protein with an intracellular domain well conserved between CD95 and tumor necrosis factor receptor I, another apoptosis-inducing protein. Because of its functional importance, this domain was designated the death domain. We describe the molecular analysis of the CD95 death domain in a family with autoimmune lymphoproliferative syndrome (Canale-Smith syndrome), T-cell lymphoma, and Hodgkin's disease. A functional defect in apoptosis was detected in cells from the index patient, a 5-year-old girl suffering from Canale-Smith syndrome and a T-cell lymphoma, as well as in her father, who had a history of splenomegaly and mild hemolysis, and her paternal uncle who had been cured of Hodgkin's disease (HD). Expansion of double-negative T cells (CD4-CD8-) was only seen in the index patient. All family members with a functional defect in apoptosis were heterozygous for a point mutation in the death domain of CD95 (A1009G, E256G). We conclude that, within the same family, a defect in apoptosis due to a mutation in the CD95 death domain can be associated with diverse clinical phenotypes, including mild, reversible symptoms and different malignancies.
authors.affiliation: University Children's Hospital Freiburg, Germany. peters@kklzoo.ukl.uni-freiburg.de
authors.forename: A M
authors.initials: AM
authors.lastname: Peters
authors.forename: B
authors.initials: B
authors.lastname: Kohfink
authors.forename: H
authors.initials: H
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Griesinger
authors.forename: B
authors.initials: B
authors.lastname: Wörmann
authors.forename: M
authors.initials: M
authors.lastname: Gahr
authors.forename: J
authors.initials: J
authors.lastname: Roesler
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D001483:Base Sequence; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D019014:fas Receptor / Q000235:genetics*
chemical_list: D017931:DNA Primers; D019014:fas Receptor