Age of onset in familial adenomatous polyposis: Heterogeneity within families and among APC mutations

S. Presciuttini, L. Varesco, P. Sala, V. Gismondi, C. Rossetti, A. Bafico, G. B. Ferrara, L. Bertario

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Heterogeneity among and within FAP pedigrees for the age of symptom onset and the age at death from colorectal cancer was studied in a sample of 583 patients of the Italian Polyposis Registry. The among pedigree variation was largely explained by clustering of families in two groups, 'early FAP' (most colorectal cancer deaths below 45 years of age) and 'late FAP' families (most deaths above age 45). The within-family variation was explained by a marked phenomenon of anticipation (15 years per generation, on the average), possibly not due to ascertainment bias. We then considered the pedigrees with identified mutation in the APC gene. Six families shared a common deletion at codon 1309 and showed the early FAP phenotype. Two families shared a mutation at codon 1061 and revealed the late FAP phenotype. Another two families (codons 453 and 302) clustered with the late FAP group, whereas a family with mutation at codon 835 clustered with the early FAP group. We suggest that there are at least two classes of mutations in the APC gene with different consequences at the phenotypic level. It seems that there are several critical points within the APC protein sequence at which truncation causes a more aggressive disease than truncation at other points.

Original languageEnglish
Pages (from-to)331-342
Number of pages12
JournalAnnals of Human Genetics
Issue number4
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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