Molecular diagnosis of familial adenomatous polyposis

N Engl J Med. 1993 Dec 30;329(27):1982-7. doi: 10.1056/NEJM199312303292702.


Background: Familial adenomatous polyposis is an inherited disease characterized by multiple colorectal tumors. The diagnosis has classically been based on the detection of multiple colorectal adenomas. The recent identification of germline mutations of the APC gene in patients with familial adenomatous polyposis makes presymptomatic molecular diagnosis possible, but the widespread distribution of the many mutations within this very large gene have heretofore made the search for such mutations impractical. We describe a novel approach that allows molecular genetic diagnosis in the majority of patients with the disease.

Methods: We screened 62 unrelated patients from the Johns Hopkins Familial Adenomatous Polyposis Registry for germline APC mutations. Primary screening was accomplished by analysis of protein synthesized in vitro from surrogate APC genes. In addition, the relative amount of transcript from each APC allele was determined with an allele-specific--expression assay.

Results: The protein assay revealed truncated protein in 51 of the 62 patients (82 percent). In 3 of the 11 remaining patients, the allele-specific--expression assay revealed significantly reduced expression of one allele of the APC gene. The use of these two assays in combination successfully identified germline APC mutations in 87 percent of the 62 patients.

Conclusions: The protein and allele-specific--expression assays provide a practical and sensitive method for molecular diagnosis of familial adenomatous polyposis. This approach will facilitate care, allowing routine testing of subjects at risk and genetic confirmation of spontaneous mutations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli / diagnosis*
  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli Protein
  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Female
  • Genes, APC*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / analysis
  • Polymerase Chain Reaction*
  • Transcription, Genetic


  • Adenomatous Polyposis Coli Protein
  • Neoplasm Proteins