Heterogeneous molecular mechanisms underlie attenuated familial adenomatous polyposis

摘要: Purpose: Familial adenomatous polyposis is a phenotypically heterogeneous disease predisposing to colorectal cancer. It dominantly transmitted, when associated with the APC gene, and recessively inherited, MUTYH gene. We searched for germline alterations in Italian Greek patients attenuated polyposis, phenotypic variant whose genetic cause remains unknown many cases. Methods: studied 26 unrelated (and 16 relatives) multiple adenomas (3–100, by endoscopic analysis) that had screened mutation-negative protein truncation test. rearrangements multiplex ligation-dependent probe amplification mutations sequencing. performed screening of five recurrent pathogenic 501 144 controls. Results: One patient proved carry an whole-gene deletion; 4 25 (16%) showed biallelic 3 (12%) monoallelic mutations. In three heterozygous subjects no pathogenetic variants were found OGG1, MTH1, APE1, MSH2, MSH6 genes. Frequency assessment healthy only Y165C G382D reach subpolymorphic frequency. Conclusion: Attenuated without “conventional” are genetically heterogeneous, phenotype not directly related defect. Therefore, families' appropriate management requires accurate clinical investigation.