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

ABSTRACT: Truncating mutations in the AXIN2 gene, a key regulator of ?-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 ?-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.

SUBMITTER: Rivera B

PROVIDER: S-EPMC3925274 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Rivera B B Perea J J Sánchez E E Villapún M M Sánchez-Tomé E E Mercadillo F F Robledo M M Benítez J J Urioste M M

European journal of human genetics : EJHG 20130710 3

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, ...[more]

PMID: 23838596

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Project description:IntroductionAn analysis was made of three different syndromes associated with p63 gene mutations, known as ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC), ankyloblepharon-ectodermal dysplasia clefting syndrome (AEC or Hay-Wells) and Rapp-Hodgkin syndrome (RHS). The postoperative complications associated with their cleft reconstructions were also evaluated.Materials and methodsExtensive demographic information, in particular of the clinical appearances, associated malformations, and the types and complications of the reconstructive surgical procedures, were recorded of these syndromic cases occurring in a database of 3621 facial cleft deformity patients. The data was analyzed using the Microsoft Excel program.ResultsA total of 10 (0.28%) cases of p63 associated syndromes were recorded: EEC (6), RHS (3), and AEC (1). The following clinical cleft appearances were noted - EEC = 6: CLA 1 -right side unilateral (female); CLAP 4 - right side (1) + left side (1) unilateral (male + female); bilateral (2) (males); hPsP 1 (female) (divided in 3 Black, 2 White, 1 Indian); RHS = 3: CLAP 2 (White males); hPsP 1 (White female); AEC = 1: CLAP bilateral (White male). Other features of the syndromes were: skin, hand, foot, tooth, hair and nail involvement, and light sensitivity. Postoperative complications included: (i) stenosis of nasal opening, especially after reconstruction of the bilateral cleft lip and the columella lengthening (2 cases), (ii) premaxilla-prolabium fusion (2 cases), (iii) repeated occurrence of oro-nasal fistula in the hard palate (4 cases), and (iv) dysgnathial development of midfacial structures (3 cases).DiscussionThree different p63 associated syndromes (EEC, AEC, and RHS) were diagnosed (0.27% of the total facial cleft deformities database). The majority of the cases presented with a bilateral CLAP in males only. A number of females and males had unilateral CLA. The hPsP-cleft was recorded in females only. The associated ectodermal component most probably had a profoundly negative influence on postoperatively wound healing, which was observed in particular at the nasal openings, the premaxilla sulcus and in the hard palate mucosa. The reconstruction of p63 associated syndromes is a greater challenge than the usual cleft reconstruction to the surgeon.

Dataset Information

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

Publications

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

Similar Datasets

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