PMID- 18830229
OWN - NLM
STAT- MEDLINE
DCOM- 20090423
LR  - 20211203
IS  - 1476-5438 (Electronic)
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 17
IP  - 3
DP  - 2009 Mar
TI  - Missense mutations to the TSC1 gene cause tuberous sclerosis complex.
PG  - 319-28
LID - 10.1038/ejhg.2008.170 [doi]
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised 
      by the development of hamartomas in a variety of organs and tissues. The disease 
      is caused by mutations in either the TSC1 gene on chromosome 9q34 or the TSC2 
      gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, 
      interact to form a protein complex that inhibits signal transduction to the 
      downstream effectors of the mammalian target of rapamycin (mTOR). Here we 
      investigate the effects of putative TSC1 missense mutations identified in 
      individuals with signs and/or symptoms of TSC on TSC1-TSC2 complex formation and 
      mTOR signalling. We show that specific amino-acid substitutions close to the 
      N-terminal of TSC1 reduce steady-state levels of TSC1, resulting in the 
      activation of mTOR signalling and leading to the symptoms of TSC.
FAU - Nellist, Mark
AU  - Nellist M
AD  - Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The 
      Netherlands. m.nellist@erasmusmc.nl
FAU - van den Heuvel, Diana
AU  - van den Heuvel D
FAU - Schluep, Diane
AU  - Schluep D
FAU - Exalto, Carla
AU  - Exalto C
FAU - Goedbloed, Miriam
AU  - Goedbloed M
FAU - Maat-Kievit, Anneke
AU  - Maat-Kievit A
FAU - van Essen, Ton
AU  - van Essen T
FAU - van Spaendonck-Zwarts, Karin
AU  - van Spaendonck-Zwarts K
FAU - Jansen, Floor
AU  - Jansen F
FAU - Helderman, Paula
AU  - Helderman P
FAU - Bartalini, Gabriella
AU  - Bartalini G
FAU - Vierimaa, Outi
AU  - Vierimaa O
FAU - Penttinen, Maila
AU  - Penttinen M
FAU - van den Ende, Jenneke
AU  - van den Ende J
FAU - van den Ouweland, Ans
AU  - van den Ouweland A
FAU - Halley, Dicky
AU  - Halley D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20081001
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (TSC1 protein, human)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acid Substitution
MH  - Humans
MH  - *Mutation, Missense
MH  - Pedigree
MH  - Protein Kinases/genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis/*genetics
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/*genetics/metabolism
PMC - PMC2986174
EDAT- 2008/10/03 09:00
MHDA- 2009/04/25 09:00
PMCR- 2009/03/01
CRDT- 2008/10/03 09:00
PHST- 2008/10/03 09:00 [pubmed]
PHST- 2009/04/25 09:00 [medline]
PHST- 2008/10/03 09:00 [entrez]
PHST- 2009/03/01 00:00 [pmc-release]
AID - ejhg2008170 [pii]
AID - 10.1038/ejhg.2008.170 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2009 Mar;17(3):319-28. doi: 10.1038/ejhg.2008.170. Epub 2008 Oct 
      1.