Increased spontaneous in vitro apoptosis in double negative T cells of humans with a fas/apo-1 mutation


We describe a 17 year old patient suffering from Canale-Smith syndrome (CSS) including chronic lymphadenopathy, splenomegaly, hypergammaglobulinemia and recurrent Coombs positive hemolytic crises. The parents are not consanguine, all other family members including two brothers are healthy. Peripheral blood mononuclear cells of the patient showed an increased rate of CD3 positive, CD4/CD8 double negative T-lymphocytes. In vitro assays showed these cells to have an increased rate of spontaneous apoptosis. Though expression of Fas/Apo-1 (CD95) and Fas-ligand (FasL) was detected on RNA- and protein level we found Fas/Apo-1 mediated apoptosis being significantly reduced. Sequencing of the fas/apo-1 gene proved the patient RT and his father to carry a point mutation at position 804 located in exon 9 (death domain) leading to an amino acid substitution. For developing of CSS, a fas/apo-1 mutation seems to be necessary but not sufficient. An additional independent mechanism must be involved in the pathogenesis of human lpr-phenotype.

Author information

Correspondence to Johannes Peter Haas.

Additional information

Edited by S. Nagata

Rights and permissions

Reprints and Permissions

About this article


  • Canale-Smith syndrome
  • autoimmune lymphoproliferative syndrome
  • spontaneous in vitro apoptosis
  • fas/apo-1 mutation

Further reading