PMID- 10340403
OWN - NLM
STAT- MEDLINE
DCOM- 19990607
LR  - 20191024
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 27
IP  - 5
DP  - 1999 May
TI  - 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.
PG  - 868-74
AB  - 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.
FAU - Peters, A M
AU  - Peters AM
AD  - University Children's Hospital Freiburg, Germany.
      peters@kklzoo.ukl.uni-freiburg.de
FAU - Kohfink, B
AU  - Kohfink B
FAU - Martin, H
AU  - Martin H
FAU - Griesinger, F
AU  - Griesinger F
FAU - Wormann, B
AU  - Wormann B
FAU - Gahr, M
AU  - Gahr M
FAU - Roesler, J
AU  - Roesler J
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (DNA Primers)
RN  - 0 (fas Receptor)
SB  - IM
MH  - Apoptosis/*genetics
MH  - Autoimmune Diseases/genetics/immunology/*pathology
MH  - Base Sequence
MH  - Child, Preschool
MH  - DNA Primers
MH  - Female
MH  - Hodgkin Disease/genetics/immunology/*pathology
MH  - Humans
MH  - Immunophenotyping
MH  - Lymphoma, T-Cell/genetics/immunology/*pathology
MH  - Lymphoproliferative Disorders/genetics/immunology/*pathology
MH  - Male
MH  - Pedigree
MH  - Point Mutation
MH  - fas Receptor/*genetics
EDAT- 1999/05/26 00:00
MHDA- 1999/05/26 00:01
CRDT- 1999/05/26 00:00
PHST- 1999/05/26 00:00 [pubmed]
PHST- 1999/05/26 00:01 [medline]
PHST- 1999/05/26 00:00 [entrez]
AID - S0301-472X(99)00033-8 [pii]
AID - 10.1016/s0301-472x(99)00033-8 [doi]
PST - ppublish
SO  - Exp Hematol. 1999 May;27(5):868-74. doi: 10.1016/s0301-472x(99)00033-8.