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Familial adenomatous polyposis

Part 1. Genetics

1.6. Genetic Medicine and Clinical Genetics

Basic Techniques and Approaches

  1. Madhuri R. Hegde1,
  2. C. Sue Richards2

Published Online: 15 JUL 2005

DOI: 10.1002/047001153X.g106415

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

How to Cite

Hegde, M. R. and Richards, C. S. 2005. Familial adenomatous polyposis. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. 1:1.6:89.

Author Information

  1. 1

    Baylor College of Medicine, Houston, TX, USA

  2. 2

    Oregon Health & Science University, Portland, OR, USA

Publication History

  1. Published Online: 15 JUL 2005

Abstract

Three cases of familial adenomatous polyposis (FAP) are presented to illustrate multiple genetic principles, including disease phenotype, mutational spectrum, and inheritance patterns. The first case represents the most common form, classical FAP consisting of thousands of polyps in an adolescent with a family history of colorectal cancer (CRC). Molecular analysis of the adenomatous polyposis gene (APC) using scanning and sequencing molecular methods reveals a novel insertion and deletion (indel) mutation on one allele, thus confirming the diagnosis and allowing targeted mutation analysis for at-risk family members. The second case illustrates attenuated FAP (AFAP), presenting at a later age with fewer polyps, in an individual with a family history of CRC. In this case, a full gene deletion of one allele was identified during molecular analysis using various technologies. The implications of these findings are discussed along with genetic counseling and testing for at-risk family members. The third example presents with a newborn diagnosed with Gardner syndrome and having no family history of FAP or CRC. Molecular analysis confirms the diagnosis and identifies a novel truncating nonsense mutation. Genetic testing and counseling implications for the family are discussed, including the possibility of gonadal mosaicism and de novo events. In all three cases, the molecular data are presented with a clinical interpretation. A discussion of inherited CRC and gene contributions, the clinical phenotypes of FAP and AFAP, the APC gene structure, types of mutations, gene function, molecular mechanisms, mutation analysis technologies, genetic counseling issues, and surveillance and treatment options are presented.

Keywords:

  • adenomatous polyposis coli;
  • FAP;
  • attenuated FAP (AFAP);
  • mutation analysis