Molecular, cytogenetic, and phenotypic studies of a constitutional reciprocal translocation t(5; I0)(q22; q25) responsible for familial adenomatous polyposis in a Dutch pedigree
✍ Scribed by Rob B. Van Der Luijt; Carli M. J. Tops; P. Meera Khan; Heleen M. Van Der Klift; Cor Breukel; Inge S. J. Van Leeuwen-Cornelisse; Hans G. Dauwerse; Geoffrey C. Beverstock; Ellen Van Noort; Pleun Snel; Frederik J. M. Slors; Hans F. A. Vasen; Riccardo Fodde
- Book ID
- 102846843
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 991 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
Familial adenomatous polyposis (FAP) is an inherited predisposition t o colorectal cancer caused by germline mutations in the adenomatous polyposis coli (APC) gene located on chromosome segment 5q2 I -q22. We detected a germline rearrangement of the APC gene in a Dutch FAP family by screening genomic DNA samples with APC cDNA probes. Subsequent molecular and cytogenetic studies revealed a constitutional reciprocal translocation t(5; I O)(q22;q25) that resulted in the disruption of the APC gene. Southern blot and polymorphic marker analysis indicated that part of the APC gene had been deleted. Analysis of the APC protein product indicated that the translocation breakpoint did not lead t o the formation of a detectable truncated APC protein but apparently resulted in a null allele. Evaluation of the clinical phenotypes in the patients suggested that they exhibited features of an unusual form of FAP characterized by a slightly delayed age of onset of colorectal cancer and a reduced number of colorectal polyps. The latter were mainly sessile and were located predominantly in the proximal colon. To our knowledge, this is the first description of FAP caused by a reciprocal translocation disrupting the APC gene. Genes Chromosom Cancer 13:192-202 (1995).