Novel APC Promoter and Exon 1B Deletion and Allelic Silencing in Three Mutation-Negative Classic Familial Adenomatous Polyposis Families

The ~80% of individuals with classic familial adenomatous polyposis (FAP) have detectable mutations in the coding sequence of the adenomatous polyposis coli (APC) gene. To investigate the 20% of families without detectable causative mutations, we used exome sequencing and second-generation sequencing of the APC locus including non-coding regions. We identified a novel ~11kb deletion 44kb upstream of APC that was present only in affected individuals of three kindreds. SNP analysis showed that this ~11kb deletion was accompanied by silencing of one of the APC alleles in blood-derived RNA of affected individuals.

• Study Design:
  • Mendelian
• Study Type:
  • Mendelian
• Total number of consented subjects: 8
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• Sequence Read Archive
• BioSample
• MeSH
• Gene
• PMC

Inclusion Criteria: Individuals with classic familial adenomatous polyposis were tested for known APC mutations with Colaris AP® (Myriad Genetic Laboratories). Those without detectable mutations by Colaris AP® and consenting family members were enrolled.

Exclusion Criteria: Individuals with sporadic gastrointestinal cancer or a family history of cancer not suggestive of hereditary or familial diseases were excluded.

• Primary Phenotype: Familial Adenomatous Polyposis
• Colonic Neoplasms

• APC

• Principal Investigator
  • Nicholas O. Davidson, MD. Washington University, St. Louis, MO, USA.
• Funding Source
  • 5P30 DK052574. National Institutes of Health, Bethesda, MD, USA.