The results of recent studies suggest that defective lymphocyte apoptosis caused by mutations of the Fas gene can result in a severe autoimmune lymphoproliferative syndrome (ALPS) in humans.
We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis.
Inherited mutations of the Fas/Apo1/CD95 gene, a cell-surface receptor involved in cell death signaling and in the control of self-reactivity, characterize the recently identified autoimmune lymphoproliferative syndromes.
Germline mutations in the Fas gene have been associated with autoimmune lymphoproliferative syndrome, and somatic Fas mutations have been found in multiple myeloma.
The defects in lymphocyte apoptosis that underlie the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of the CD95 (Fas) gene.
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.
Defective lymphocyte apoptosis caused by mutations of the Fas (CD95) gene has been linked in the pathogenesis of ALPS, as binding of Fas-ligand to Fas can trigger apoptosis.
Fas (CD95/Apo-1) mutations were previously reported as the genetic defect responsible for human lymphoproliferative syndrome associated with autoimmune manifestations (also known as autoimmune lymphoproliferative syndrome or Canale-Smith syndrome).
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.
The human disease, Autoimmune Lymphoproliferative Syndrome (ALPS) is due to dominant-interfering mutations in the Fas/APO-1/CD95 receptor and other components of the death pathway.
Most humans with autoimmune lymphoproliferative syndrome (ALPS) carry heterozygous dominant mutations in one allele of the gene encoding Fas/APO-1/CD95.
These data suggest that intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting death-domain interactions with the signaling protein FADD/MORT1.
Fas (CD95/Apo-1) mutations were previously reported as the genetic defect responsible for human lymphoproliferative syndrome associated with autoimmune manifestations (also known as autoimmune lymphoproliferative syndrome or Canale-Smith syndrome).