PMID- 10515860
OWN - NLM
STAT- MEDLINE
DCOM- 19991122
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 8
DP  - 1999 Oct 15
TI  - Lymphoproliferative syndrome with autoimmunity: A possible genetic basis for
      dominant expression of the clinical manifestations.
PG  - 2575-82
AB  - 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 have identified 14 new heterozygous Fas mutations.
      Analysis of patients and families allow us to further dissect this syndrome with 
      regards to the relationship between Fas mutations, inheritance pattern, and
      phenotype as observed on long-term follow-up. In vitro studies show that
      lymphocytes from all Fas mutant carriers exhibit a Fas-antibody-induced apoptosis
      defect. However, among the 8 inherited mutations, 4 of 4 Fas missense mutations
      were associated with high clinical penetrance, whereas 3 of 4 mutations leading
      to a truncated Fas product were associated with variable clinical penetrance.
      This suggests that a second defect, in another yet undefined factor involved in
      apoptosis and/or lymphoproliferation control, is necessary to induce full
      clinical expression of the disease. These results also indicate that the
      currently available antibody-mediated in vitro apoptosis assay does not
      necessarily reflect the in vivo ability of abnormal Fas molecules to trigger
      lymphocyte death. In addition, we found that lymphoproliferative manifestations
      resolved with age, whereas immunological disorders [ie, hypergammaglobulinemia
      and detection of TcR alphabeta(+) CD4(-) CD8(-) lymphocytes] persisted. This
      observation suggests that Fas-mediated apoptosis plays a more important role in
      lymphocyte homeostasis in early childhood than later on in life.
FAU - Rieux-Laucat, F
AU  - Rieux-Laucat F
AD  - Department of Pediatric Immunology, Unit INSERM U429, Hopital
      Necker-Enfants-Malades, Paris, France. rieux@necker.fr
FAU - Blachere, S
AU  - Blachere S
FAU - Danielan, S
AU  - Danielan S
FAU - De Villartay, J P
AU  - De Villartay JP
FAU - Oleastro, M
AU  - Oleastro M
FAU - Solary, E
AU  - Solary E
FAU - Bader-Meunier, B
AU  - Bader-Meunier B
FAU - Arkwright, P
AU  - Arkwright P
FAU - Pondare, C
AU  - Pondare C
FAU - Bernaudin, F
AU  - Bernaudin F
FAU - Chapel, H
AU  - Chapel H
FAU - Nielsen, S
AU  - Nielsen S
FAU - Berrah, M
AU  - Berrah M
FAU - Fischer, A
AU  - Fischer A
FAU - Le Deist, F
AU  - Le Deist F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (fas Receptor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Amino Acid Substitution
MH  - Apoptosis
MH  - Autoimmune Diseases/*genetics/immunology
MH  - Child
MH  - Exons/genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Genes, Dominant
MH  - Genetic Heterogeneity
MH  - Genetic Predisposition to Disease
MH  - Heterozygote
MH  - Humans
MH  - Hypergammaglobulinemia/etiology
MH  - Hypersplenism/etiology/surgery
MH  - Infant
MH  - Lymphoproliferative Disorders/*genetics/immunology
MH  - Male
MH  - Point Mutation
MH  - Splenectomy
MH  - Splenomegaly/etiology/surgery
MH  - T-Lymphocytes/chemistry/pathology
MH  - Uveitis/etiology
MH  - fas Receptor/*genetics
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
AID - S0006-4971(20)71090-6 [pii]
PST - ppublish
SO  - Blood. 1999 Oct 15;94(8):2575-82.