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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.
Hum Mutat. 1999; 13(2):116-23.HM

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.

Authors+Show Affiliations

Division of Experimental Oncology A, Istituto Nazionale Tumori, Milano, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10094547

Citation

Giarola, M, et al. "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." Human Mutation, vol. 13, no. 2, 1999, pp. 116-23.
Giarola M, Stagi L, Presciuttini S, et al. 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. Hum Mutat. 1999;13(2):116-23.
Giarola, M., Stagi, L., Presciuttini, S., Mondini, P., Radice, M. T., Sala, P., Pierotti, M. A., Bertario, L., & Radice, P. (1999). 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. Human Mutation, 13(2), 116-23.
Giarola M, et al. 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. Hum Mutat. 1999;13(2):116-23. PubMed PMID: 10094547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Giarola,M, AU - Stagi,L, AU - Presciuttini,S, AU - Mondini,P, AU - Radice,M T, AU - Sala,P, AU - Pierotti,M A, AU - Bertario,L, AU - Radice,P, PY - 1999/3/27/pubmed PY - 2000/6/22/medline PY - 1999/3/27/entrez SP - 116 EP - 23 JF - Human mutation JO - Hum Mutat VL - 13 IS - 2 N2 - 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. SN - 1059-7794 UR - https://www.unboundmedicine.com/medline/citation/10094547/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_ L2 - https://doi.org/10.1002/(SICI)1098-1004(1999)13:2<116::AID-HUMU3>3.0.CO;2-2 DB - PRIME DP - Unbound Medicine ER -