PMID- 18456716
OWN - NLM
STAT- MEDLINE
DCOM- 20081210
LR  - 20191210
IS  - 1468-6244 (Electronic)
IS  - 0022-2593 (Linking)
VI  - 45
IP  - 10
DP  - 2008 Oct
TI  - Contribution of PTEN large rearrangements in Cowden disease: a multiplex 
      amplifiable probe hybridisation (MAPH) screening approach.
PG  - 657-65
LID - 10.1136/jmg.2008.058131 [doi]
AB  - BACKGROUND: Cowden disease is an autosomal dominant syndrome predisposing to 
      cancer and characterised by the occurrence throughout life of hyperplastic, 
      hamartomatous and tumoural lesions affecting various organs. In 60-80% of 
      patients a germline intragenic point mutation of the PTEN tumour suppressor gene 
      is identified, but at least 20% of patients with a well characterised phenotype 
      remain without any identified mutation. METHODS: To evaluate the impact of large 
      rearrangement involving the PTEN locus in Cowden disease, we analysed by a 
      multiplex amplifiable probe hybridisation (MAPH) technique 80 unrelated patients 
      referred for diagnosed or suspected Cowden disease, and in whom no PTEN point 
      mutation was detected by a denaturing gradient gel electrophoresis (DGGE) 
      screening. RESULTS: Four heterozygous genomic deletions involving the PTEN gene 
      were identified. These deletions ranged from 13.6-662 kb and are restricted to 
      the PTEN locus in two cases. In the two other cases, the deletion encompassed 
      PTEN and either two or three contiguous genes without any obvious phenotypic 
      effect, except a possible consequence of PAPSS2 haploinsufficiency on bone 
      growth. Sequence analysis of the four deleted alleles did not reveal identity or 
      sequence homology at the two breakpoints of a same allele, suggesting that a 
      mechanism such as non-homologous recombination of the breakage and reunion type 
      could lead to the occurrence of these deletions. CONCLUSION: Large rearrangements 
      of the PTEN gene can be involved as causing mutation in Cowden disease and MAPH 
      is an efficient screening methodology to detect such a genetic alteration.
FAU - Chibon, F
AU  - Chibon F
AD  - Laboratoire de genetique moleculaire, Institut Bergonie, 229, cours de l'Argonne, 
      33076 Bordeaux cedex, France.
FAU - Primois, C
AU  - Primois C
FAU - Bressieux, J-M
AU  - Bressieux JM
FAU - Lacombe, D
AU  - Lacombe D
FAU - Lok, C
AU  - Lok C
FAU - Mauriac, L
AU  - Mauriac L
FAU - Taieb, A
AU  - Taieb A
FAU - Longy, M
AU  - Longy M
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080502
PL  - England
TA  - J Med Genet
JT  - Journal of medical genetics
JID - 2985087R
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Adult
MH  - Female
MH  - *Gene Deletion
MH  - Genetic Testing/*methods
MH  - Hamartoma Syndrome, Multiple/*genetics
MH  - Humans
MH  - Male
MH  - Nucleic Acid Hybridization
MH  - PTEN Phosphohydrolase/*genetics
MH  - Phenotype
EDAT- 2008/05/06 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/05/06 09:00
PHST- 2008/05/06 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/05/06 09:00 [entrez]
AID - jmg.2008.058131 [pii]
AID - 10.1136/jmg.2008.058131 [doi]
PST - ppublish
SO  - J Med Genet. 2008 Oct;45(10):657-65. doi: 10.1136/jmg.2008.058131. Epub 2008 May 
      2.