Human Genetics

, Volume 124, Issue 5, pp 535–541

A large novel deletion in the APC promoter region causes gene silencing and leads to classical familial adenomatous polyposis in a Manitoba Mennonite kindred

  • George S. Charames
  • Lily Ramyar
  • Angela Mitri
  • Terri Berk
  • Hong Cheng
  • Jack Jung
  • Patricia Bocangel
  • Bernie Chodirker
  • Cheryl Greenberg
  • Elizabeth Spriggs
  • Bharati Bapat
Original Investigation

DOI: 10.1007/s00439-008-0579-4

Cite this article as:
Charames, G.S., Ramyar, L., Mitri, A. et al. Hum Genet (2008) 124: 535. doi:10.1007/s00439-008-0579-4

Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by the inheritance of germline mutations in the APC tumour suppressor gene. The vast majority of these are nonsense and frameshift mutations resulting in a truncated protein product and abnormal function. While APC promoter hypermethylation has been previously documented, promoter-specific deletion mutations have not been reported. In a large Canadian Mennonite polyposis kindred, we identified a large novel germline deletion in the APC promoter region by linkage analysis and MLPA. By RT-PCR and sequence analysis, this mutation was found to result in transcriptional silencing of the APC allele. A few genetic disorders have been characterized as over-represented in the Manitoba Mennonite population, however, the incidence of cancer has not been recognized as increased in this population as compared to other Manitoba ethnic groups. This study strengthens the likelihood that this novel APC promoter mutation is linked to this unique population as a founder mutation.

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • George S. Charames
    • 1
    • 2
    • 3
  • Lily Ramyar
    • 2
  • Angela Mitri
    • 2
  • Terri Berk
    • 4
  • Hong Cheng
    • 2
  • Jack Jung
    • 5
    • 6
  • Patricia Bocangel
    • 7
  • Bernie Chodirker
    • 8
  • Cheryl Greenberg
    • 8
  • Elizabeth Spriggs
    • 8
    • 9
  • Bharati Bapat
    • 1
    • 2
    • 3
  1. 1.Samuel Lunenfeld Research Institute, Mount Sinai HospitalTorontoCanada
  2. 2.Department of Pathology and Laboratory MedicineMount Sinai HospitalTorontoCanada
  3. 3.Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  4. 4.Dr. Zane Cohen Digestive Diseases Clinical Research CentreMount Sinai HospitalTorontoCanada
  5. 5.Medical Genetics Program of Southwestern OntarioChildren’s HospitalLondonCanada
  6. 6.Division of Medical Genetics, Department of Paediatrics, Schulich School of Medicine and DentistryUniversity of Western OntarioLondonCanada
  7. 7.WRHA Program of Genetics and Metabolism, Health Sciences CentreWinnipegCanada
  8. 8.Departments of Biochemistry and Medical Genetics and Pediatrics & Child HealthUniversity of ManitobaWinnipegCanada
  9. 9.Molecular Diagnostic Laboratory, Diagnostic Services of ManitobaWinnipegCanada