PMID- 17604324
OWN - NLM
STAT- MEDLINE
DCOM- 20080128
LR  - 20080703
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 57
IP  - 1
DP  - 2008 Jan
TI  - Somatic APC mosaicism: an underestimated cause of polyposis coli.
PG  - 71-6
AB  - BACKGROUND: The patient with 10 or more adenomas in the colon poses a diagnostic 
      challenge. Beside germline mutations in the APC and MUTYH genes, only four cases 
      of mosaic APC mutations have been reported. AIM: Given the relatively high 
      frequency of de novo APC mutations in familial adenomatous polyposis (FAP), an 
      investigation was carried out into whether the proportion of somatic mosaic APC 
      mutations is currently underestimated. METHODS: Between 1 January 1994 and 31 
      December 2005 germline mutation analysis was performed in 599 consecutive index 
      patients with polyposis coli referred for diagnostic APC scanning using a 
      combination of denaturing gradient gel electrophoresis (DGGE) and protein 
      truncation test (PTT). Variants were analysed by direct sequencing with primers 
      flanking those used for DGGE and PTT, and quantified using pyrosequencing. 
      RESULTS: Scrutinizing the molecular genetic results and family data of 242 index 
      patients with pathogenic APC mutations led to the identification of 10 mosaic 
      cases (4%). C>T transitions were observed in CGA sites in four of the 10 cases 
      with somatic mosaicism, which is significantly more than 26 of the 232 non-mosaic 
      cases (p = 0.02). Phenotypes of patients with somatic mosaicism ranged from an 
      attenuated form of polyposis coli to florid polyposis with major extracolonic 
      manifestations. CONCLUSIONS: Mosaicism occurs in a significant number of APC 
      mutations and it is estimated that one-fifth of the de novo cases of FAP are 
      mosaic. Clinically, the severity of manifestations in offspring and the 
      recurrence risk for siblings of apparently sporadic polyposis patients may be 
      underestimated due to parental APC mosaicism.
FAU - Hes, F J
AU  - Hes FJ
AD  - Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, 
      The Netherlands. f.j.hes@lumc.nl
FAU - Nielsen, M
AU  - Nielsen M
FAU - Bik, E C
AU  - Bik EC
FAU - Konvalinka, D
AU  - Konvalinka D
FAU - Wijnen, J T
AU  - Wijnen JT
FAU - Bakker, E
AU  - Bakker E
FAU - Vasen, H F A
AU  - Vasen HF
FAU - Breuning, M H
AU  - Breuning MH
FAU - Tops, C M J
AU  - Tops CM
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20070629
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
SB  - IM
CIN - Gut. 2008 Jan;57(1):10-2. PMID: 18094199
MH  - Adenomatous Polyposis Coli/*genetics
MH  - Adult
MH  - Aged
MH  - Cohort Studies
MH  - Female
MH  - *Genes, APC
MH  - Genotype
MH  - Germ-Line Mutation
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mosaicism
MH  - Pedigree
MH  - Phenotype
EDAT- 2007/07/03 09:00
MHDA- 2008/01/29 09:00
CRDT- 2007/07/03 09:00
PHST- 2007/07/03 09:00 [pubmed]
PHST- 2008/01/29 09:00 [medline]
PHST- 2007/07/03 09:00 [entrez]
AID - gut.2006.117796 [pii]
AID - 10.1136/gut.2006.117796 [doi]
PST - ppublish
SO  - Gut. 2008 Jan;57(1):71-6. doi: 10.1136/gut.2006.117796. Epub 2007 Jun 29.