MOLECULAR, CYTOGENETIC, AND PHENOTYPIC STUDIES OF A CONSTITUTIONAL RECIPROCAL TRANSLOCATION T(5-10)(Q22-Q25) RESPONSIBLE FOR FAMILIAL ADENOMATOUS POLYPOSIS IN A DUTCH PEDIGREE

Familiar adenomatous polyposis (FAP) is an inherited predisposition to colorectal cancer caused by germline mutations in the adenomatous pol yposis coli (APC) gene located on chromosome segment 5921-q22, We dete cted a germline rearrangement of the APC gene in a Dutch FAP family by screening genomic DNA samples with APC cDNA probes, Subsequent molecu lar and cytogenetic studies revealed a constitutional reciprocal trans location t(5;10)(q22;q25) that resulted in the disruption of the APC g ene, 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 nor lead to the forma tion of a detectable truncated APC protein but apparently resulted in a null allele. Evaluation of the clinical phenotypes in the patients s uggested that they exhibited features of an unusual form of FAP charac terized by a slightly delayed age of onset of colorectal cancer and a reduced number of colorectal polyps. The latter were mainly sessile an d were located predominantly in the proximal colon. To our knowledge, this is the first description of FAP caused by a reciprocal translocat ion disrupting the APC gene. (C) 1995 Wiley-Liss, Inc.