PMID- 16446975
OWN - NLM
STAT- MEDLINE
DCOM- 20070201
LR  - 20181113
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 119
IP  - 3
DP  - 2006 Apr
TI  - Genetic alterations in caspase-10 may be causative or protective in autoimmune 
      lymphoproliferative syndrome.
PG  - 284-94
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is characterized by 
      lymphadenopathy, elevated numbers of T cells with alphabeta-T cell receptors but 
      neither CD4 nor CD8 co-receptors, and impaired lymphocyte apoptosis in vitro. 
      Defects in the Fas receptor are the most common cause of ALPS (ALPS Ia), but in 
      rare cases other apoptosis proteins have been implicated, including caspase-10 
      (ALPS II). We investigated the role of variants of caspase-10 in ALPS. Of 32 
      unrelated probands with ALPS who did not have Fas defects, two were heterozygous 
      for the caspase-10 missense mutation I406L. Like the previously reported ALPS 
      II-associated mutation L285F, I406L impaired apoptosis when transfected alone and 
      dominantly inhibited apoptosis mediated by wild type caspase-10 in a 
      co-transfection assay. Other variants in caspase-10, V410I and Y446C, were found 
      in 3.4 and 1.6% of chromosomes in Caucasians, and in 0.5 and <0.5% of African 
      Americans, respectively. In contrast to L285F and I406L, these variants had no 
      dominant negative effect in co-transfection assays into the H9 lymphocytic cell 
      line. We found healthy individuals homozygous for V410I, challenging the earlier 
      suggestion that homozygosity for V410I alone causes ALPS. Moreover, an 
      association analysis suggested protection from severe disease by caspase-10 V410I 
      in 63 families with ALPS Ia due to dominant Fas mutations (P<0.05). Thus, 
      different genetic variations in caspase-10 can produce contrasting phenotypic 
      effects.
FAU - Zhu, Shigui
AU  - Zhu S
AD  - Genetics and Molecular Biology Branch, National Human Genome Research Institute, 
      NIH, DHHS, Bethesda, MD 20892, USA.
FAU - Hsu, Amy P
AU  - Hsu AP
FAU - Vacek, Marla M
AU  - Vacek MM
FAU - Zheng, Lixin
AU  - Zheng L
FAU - Schaffer, Alejandro A
AU  - Schaffer AA
FAU - Dale, Janet K
AU  - Dale JK
FAU - Davis, Joie
AU  - Davis J
FAU - Fischer, Roxanne E
AU  - Fischer RE
FAU - Straus, Stephen E
AU  - Straus SE
FAU - Boruchov, Donna
AU  - Boruchov D
FAU - Saulsbury, Frank T
AU  - Saulsbury FT
FAU - Lenardo, Michael J
AU  - Lenardo MJ
FAU - Puck, Jennifer M
AU  - Puck JM
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20060131
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - EC 3.4.22.- (Caspase 10)
RN  - EC 3.4.22.63 (CASP10 protein, human)
SB  - IM
MH  - Autoimmune Diseases/*etiology
MH  - Caspase 10/*genetics/metabolism
MH  - Cells, Cultured
MH  - Child
MH  - Child, Preschool
MH  - Family
MH  - Female
MH  - Genetic Testing
MH  - Genetic Variation
MH  - Humans
MH  - Infant
MH  - Jurkat Cells
MH  - Lymphoproliferative Disorders/*etiology
MH  - Male
MH  - Phenotype
MH  - Syndrome
MH  - Transfection
EDAT- 2006/02/01 09:00
MHDA- 2007/02/03 09:00
CRDT- 2006/02/01 09:00
PHST- 2005/10/02 00:00 [received]
PHST- 2006/01/04 00:00 [accepted]
PHST- 2006/02/01 09:00 [pubmed]
PHST- 2007/02/03 09:00 [medline]
PHST- 2006/02/01 09:00 [entrez]
AID - 10.1007/s00439-006-0138-9 [doi]
PST - ppublish
SO  - Hum Genet. 2006 Apr;119(3):284-94. doi: 10.1007/s00439-006-0138-9. Epub 2006 Jan 
      31.