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Eur J Hum Genet. 2014 Mar;22(3):423-6. doi: 10.1038/ejhg.2013.146. Epub 2013 Jul 10.

A novel AXIN2 germline variant associated with attenuated FAP without signs of oligondontia or ectodermal dysplasia.

Author information

1
Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
2
General Surgery Service, Hospital 12 de Octubre, Madrid, Spain.
3
Gastro-Endoscope Service, Clínica Ntra. Sra. Del Rosario, Madrid, Spain.
4
1] Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain [2] Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
5
1] Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain [2] Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
6
1] Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain [2] Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain.

Abstract

Truncating mutations in the AXIN2 gene, a key regulator of β-catenin degradation in the Wnt pathway, have been reported in three families with gastrointestinal adenomatous polyposis and features of ectodermal dysplasia. However, the role of AXIN2 in familial adenomatous polyposis (FAP) syndrome is not completely understood. We performed an in-depth study of APC and MUTYH, and ruled out their implication in 23 FAP families. We then investigated the role of other genes involved in the Wnt pathway, including AXIN2, and identified a novel missense variant in AXIN2 in one family with attenuated FAP. Carriers of the variant exhibited a variable number of polyps but none showed any sign of ectodermal dysplasia. We have demonstrated the pathogenicity of this novel variant by establishing its low frequency in controls as well as by LOH analysis, a segregation study, and immunofluorescent staining of AXIN2 and β-catenin proteins. This report expands the phenotype known to be related to AXIN2 alterations and raises the question of whether to screen AXIN2 in FAP cases negative for alterations in APC and MUTYH.

PMID:
23838596
PMCID:
PMC3925274
DOI:
10.1038/ejhg.2013.146
[Indexed for MEDLINE]
Free PMC Article

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