PMID- 10234502
OWN - NLM
STAT- MEDLINE
DCOM- 19990628
LR  - 20161124
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 7
IP  - 3
DP  - 1999 Apr
TI  - Novel PTEN mutations in patients with Cowden disease: absence of clear
      genotype-phenotype correlations.
PG  - 267-73
AB  - Cowden disease (CD) is characterised by multiple hamartomas in a variety of
      tissues. The pathological hallmark is the presence of a number of trichilemmomas.
      Several neurological symptoms are also part of CD with megalencephaly and
      Lhermitte-Duclos disease (LDD) as the most important features. Early recognition 
      of CD patients is important because of the increased risk of developing
      malignancies. Breast cancer is the most frequent malignancy, but also urogenital,
      digestive tract, and thyroid cancers are found with higher frequencies. CD was
      localised to chromosome 10q23 and the PTEN gene (also known as MMAC1 or TEP1) was
      shown to be involved. Germline mutations were identified in both familial and
      sporadic CD patients. We identified eight PTEN mutations, of which seven were
      novel, in 13 CD patients. Combined with previous data we have identified 17
      independent CD mutations. Gross DNA alterations in CD patients were not detected.
      Genotype-phenotype relations are discussed. The only correlation suggested to
      exist is that missense mutations are not detected in LDD patients. However,
      larger numbers are needed to confirm this. Association of PTEN mutations and the 
      occurrence of malignant breast disease found in an earlier study cannot be
      confirmed. Clinical features of five CD patients without a PTEN mutation in the
      coding sequence do not differ from CD patients with a PTEN mutation. Furthermore,
      it is likely that we have identified the majority of CD patients in the
      Netherlands. From this we estimate that CD has a prevalence of about 1 in 250,000
      in the Dutch population with a low mutation frequency.
FAU - Nelen, M R
AU  - Nelen MR
AD  - Department of Neurology, University Hospital Nijmegen, The Netherlands.
      m.nelen@czzorlnm.azn.nl
FAU - Kremer, H
AU  - Kremer H
FAU - Konings, I B
AU  - Konings IB
FAU - Schoute, F
AU  - Schoute F
FAU - van Essen, A J
AU  - van Essen AJ
FAU - Koch, R
AU  - Koch R
FAU - Woods, C G
AU  - Woods CG
FAU - Fryns, J P
AU  - Fryns JP
FAU - Hamel, B
AU  - Hamel B
FAU - Hoefsloot, L H
AU  - Hoefsloot LH
FAU - Peeters, E A
AU  - Peeters EA
FAU - Padberg, G W
AU  - Padberg GW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Female
MH  - Genotype
MH  - Hamartoma Syndrome, Multiple/enzymology/*genetics
MH  - Humans
MH  - Male
MH  - PTEN Phosphohydrolase
MH  - Phenotype
MH  - Phosphoric Monoester Hydrolases/*genetics
MH  - *Tumor Suppressor Proteins
EDAT- 1999/05/11 00:00
MHDA- 1999/05/11 00:01
CRDT- 1999/05/11 00:00
PHST- 1999/05/11 00:00 [pubmed]
PHST- 1999/05/11 00:01 [medline]
PHST- 1999/05/11 00:00 [entrez]
AID - 10.1038/sj.ejhg.5200289 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 1999 Apr;7(3):267-73. doi: 10.1038/sj.ejhg.5200289.