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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
Author(s) -
Giarola Monica,
Stagi Lisa,
Presciuttini Silvano,
Mondini Patrizia,
Radice Maria T.,
Sala Paola,
Pierotti Marco A.,
Bertario Lucio,
Radice Paolo
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1999)13:2<116::aid-humu3>3.0.co;2-2
Subject(s) - biology , familial adenomatous polyposis , genetics , phenotype , mutation , gene , adenomatous polyposis coli , colorectal cancer , cancer
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. Hum Mutat 13:116–123, 1999. © 1999 Wiley‐Liss, Inc.