Screening for mutations of the APC gene in 66 italian familial adenomatous polyposis patients: Evidence for phenotypic differences in cases with and without identified mutation

Monica Giarola, Lisa Stagi, Silvano Presciuttini, Patrizia Mondini, Maria T. Radice, Paola Sala, Marco A. Pierotti, Lucio Bertario, Paolo Radice

Research output: Contribution to journalArticle

Abstract

Germline mutations in the APC gene are responsible for familial adenomatous polyposis (FAP), a dominantly inherited syndrome characterized by the development of hundreds to thousands of polyps in the colon and in the rectum of affected individuals and by variable extracolonic manifestations (gastric and duodenal polyps, osteomas, retinal lesions, and desmoid tumors). Through the combined use of single-strand conformation polymorphism (SSCP) analysis and the protein truncation test (PTT), we have screened 66 Italian FAP patients and found 29 different APC mutations in a total of 34 cases. Of the identified mutations, 15 were nonsense, 12 were 1- to 5-bp deletions or insertions and two were complex rearrangements, all leading to the formation of premature stop codons. Only 10 mutations had been already previously described at the germline level, confirming the high heterogeneity of the APC mutational spectrum. The mean age of diagnosis in mutation positive cases and their affected relatives was significantly lower than in cases without identified mutation (30.6 vs 39.1 years, respectively; p = 0.003). In addition, among patients without a family history of polyposis, all mutation- positive cases displayed at least one of the extracolonic manifestations usually associated with FAP, whereas in one-half of the cases without identified mutation, none of these phenotypes was observed. Although a fraction of apparently mutation-negative cases were likely to be due to limitations of the mutation screening strategy, our results suggest, in agreement with previous reports, that allelic and/or genetic heterogeneity might be responsible for the phenotypic variability observed in FAP patients.

Original languageEnglish
Pages (from-to)116-123
Number of pages8
JournalHuman Mutation
Volume13
Issue number2
DOIs
Publication statusPublished - 1999

Keywords

  • APC
  • Familial adenomatous polyposis
  • Germline mutations
  • Phenotypic variability

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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