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    DNA Repair (Amst). 2007 Mar 1;6(3):274-9. Epub 2006 Dec 11.

    MUTYH-associated polyposis--from defect in base excision repair to clinical genetic testing.

    Source

    Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. cheadlejp@cardiff.ac.uk

    Abstract

    Established predisposition genes account for only a small proportion of familial colorectal cancer. Recently, it has been shown that germline mutations in MUTYH predispose to MUTYH-associated polyposis (MAP), an autosomal recessive disorder characterised by multiple colorectal adenomas and carcinomas. MUTYH functions as a base excision repair DNA glycosylase that excises adenines misincorporated opposite 8-oxo-7,8-dihydro-2'-deoxyguanosine, one of the most stable products of oxidative DNA damage. It is the failure to correct this mispair that is thought to give rise to the characteristic signature of G:C-->T:A mutations found in MAP-associated tumours. Here, we review the germline mutation spectrum at the MUTYH locus (comprising 30 truncating and 55 missense/inframe insertion/deletion variants) and the molecular mechanism and biochemical defect(s) underlying this disorder. We also discuss the application of molecular genetic analysis of MUTYH in clinical practice.

    PMID:
    17161978
    [PubMed - indexed for MEDLINE]

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