Gastric polyposis and desmoid tumours as a new familial adenomatous polyposis clinical variant associated with APC mutation at the extreme 3′-end. Issue 5 (7th October 2019)

• Record Type: Journal Article
• Authors: Disciglio, Vittoria; Fasano, Candida; Cariola, Filomena; Forte, Giovanna; Grossi, Valentina; Sanese, Paola; Lepore Signorile, Martina; Resta, Nicoletta; Lotesoriere, Claudio; Stella, Alessandro; Lolli, Ivan; Simone, Cristiano
• Is Part Of: Journal of medical genetics. Volume 57:Issue 5(2020)
• Page Start: 356
• Page End: 360
• Publication Date: 2019-10-07
• Subjects: APC C-terminus -- Gastric Polyposis -- Familial Adenomatous Polyposis -- Gastric Polyposis and Desmoid FAP; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2019-106299
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Germline mutations of the APC gene, which encodes a multidomain protein of 2843 amino acid residues, cause familial adenomatous polyposis (FAP). Three FAP clinical variants are correlated with the location of APC mutations: (1) classic FAP with profuse polyposis (>1000 adenomas), associated with mutations from codon 1250 to 1424; (2) attenuated FAP (<100 adenomas), associated with mutations at APC extremities (before codon 157 and after codon 1595); (3) classic FAP with intermediate colonic polyposis (100–1000 adenomas), associated with mutations located in the remaining part of APC . In an effort to decipher the clinical phenotype associated with APC C-terminal germline truncating mutations in patients with FAP, after screening APC mutations in one family whose members (n=4) developed gastric polyposis, colon oligo-polyposis and desmoid tumours, we performed a literature meta-analysis of clinically characterised patients (n=97) harbouring truncating mutations in APC C-terminus. The APC distal mutations identified in this study cluster with a phenotype characterised by colon oligo-polyposis, diffuse gastric polyposis and desmoid tumours. In conclusion, we describe a novel FAP clinical variant, which we propose to refer to as Gastric Polyposis and Desmoid FAP, that may require tailored management.