PMID- 10408777
OWN - NLM
STAT- MEDLINE
DCOM- 19991103
LR  - 20211203
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 13
IP  - 6
DP  - 1999
TI  - Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families.
PG  - 476-81
AB  - The Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder in which
      gastrointestinal hamartomatous polyposis, mucocutaneous pigmentation, and a
      predisposition for developing cancer are transmitted in an autosomal dominant
      fashion. The recently identified LKB1/STK11 gene located at chromosome 19p13.3 is
      mutated in a number of PJS pedigrees. We performed mutation analysis in 19,
      predominantly Dutch, PJS families. In 12 of these families, we identified
      LKB1/STK11 mutations, none of which has been described before. These 12 novel
      LKB1/STK11 mutations consist of one nonsense mutation, three frameshift
      deletions, three frameshift insertions, two acceptor splice site mutations, and
      three missense mutations. In addition, we detected four polymorphisms in
      LKB1/STK11. In the remaining seven PJS families, we found no apparent
      abnormalities of the LKB1/STK1I gene, which could reflect the existence of locus 
      heterogeneity in PJS. None of the mutations occurred in more than one family, and
      a number were demonstrated to have arisen de novo. The diverse array of mutations
      found, the apparent high mutation rate, as well as the existence of a possible
      second PJS locus, renders diagnostic or predictive genetic testing in individual 
      patients difficult, although future identification of additional mutations or
      even gene(s) will help in increasing the yield of direct mutation analysis.
FAU - Westerman, A M
AU  - Westerman AM
AD  - Department of Internal Medicine II, University Hospital Rotterdam Dijkzigt, The
      Netherlands.
FAU - Entius, M M
AU  - Entius MM
FAU - Boor, P P
AU  - Boor PP
FAU - Koole, R
AU  - Koole R
FAU - de Baar, E
AU  - de Baar E
FAU - Offerhaus, G J
AU  - Offerhaus GJ
FAU - Lubinski, J
AU  - Lubinski J
FAU - Lindhout, D
AU  - Lindhout D
FAU - Halley, D J
AU  - Halley DJ
FAU - de Rooij, F W
AU  - de Rooij FW
FAU - Wilson, J H
AU  - Wilson JH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (STK11 protein, human)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Base Sequence
MH  - Chromosomes, Human, Pair 19
MH  - Female
MH  - Gene Deletion
MH  - Humans
MH  - Male
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Mutation, Missense
MH  - Netherlands
MH  - Peutz-Jeghers Syndrome/*genetics
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - Protein Serine-Threonine Kinases/*genetics
EDAT- 1999/07/17 10:00
MHDA- 2000/06/22 10:00
CRDT- 1999/07/17 10:00
PHST- 1999/07/17 10:00 [pubmed]
PHST- 2000/06/22 10:00 [medline]
PHST- 1999/07/17 10:00 [entrez]
AID - 10.1002/(SICI)1098-1004(1999)13:6<476::AID-HUMU7>3.0.CO;2-2 [pii]
AID - 10.1002/(SICI)1098-1004(1999)13:6<476::AID-HUMU7>3.0.CO;2-2 [doi]
PST - ppublish
SO  - Hum Mutat. 1999;13(6):476-81. doi:
      10.1002/(SICI)1098-1004(1999)13:6<476::AID-HUMU7>3.0.CO;2-2.