Molecular, cytogenetic, and phenotypic studies of a constitutional reciprocal translocation t(5; I0)(q22; q25) responsible for familial adenomatous polyposis in a Dutch pedigree
Corresponding Author
Rob B. Van Der Luijt
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Wassenaarseweg 72, 2333 AL Leiden, The NetherlandsSearch for more papers by this authorCarli M. J. Tops
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorP. Meera Khan
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorHeleen M. Van Der Klift
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorCor Breukel
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorInge S. J. Van Leeuwen-Cornelisse
The Netherlands Foundation for the Detection of Hereditary Tumors, Leiden, The Netherlands
Search for more papers by this authorHans G. Dauwerse
Department of Clinical Cytogenetics, Leiden University Hospital, Leiden, The Netherlands
Search for more papers by this authorGeoffrey C. Beverstock
Department of Clinical Cytogenetics, Leiden University Hospital, Leiden, The Netherlands
Search for more papers by this authorEllen Van Noort
Department of Clinical Cytogenetics, Leiden University Hospital, Leiden, The Netherlands
Search for more papers by this authorPleun Snel
Department of Gastroenterology, Slotervaart Hospital, Amsterdam, The Netherlands
Search for more papers by this authorFrederik J. M. Slors
Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorHans F. A. Vasen
The Netherlands Foundation for the Detection of Hereditary Tumors, Leiden, The Netherlands
Search for more papers by this authorRiccardo Fodde
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorCorresponding Author
Rob B. Van Der Luijt
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Wassenaarseweg 72, 2333 AL Leiden, The NetherlandsSearch for more papers by this authorCarli M. J. Tops
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorP. Meera Khan
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorHeleen M. Van Der Klift
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorCor Breukel
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorInge S. J. Van Leeuwen-Cornelisse
The Netherlands Foundation for the Detection of Hereditary Tumors, Leiden, The Netherlands
Search for more papers by this authorHans G. Dauwerse
Department of Clinical Cytogenetics, Leiden University Hospital, Leiden, The Netherlands
Search for more papers by this authorGeoffrey C. Beverstock
Department of Clinical Cytogenetics, Leiden University Hospital, Leiden, The Netherlands
Search for more papers by this authorEllen Van Noort
Department of Clinical Cytogenetics, Leiden University Hospital, Leiden, The Netherlands
Search for more papers by this authorPleun Snel
Department of Gastroenterology, Slotervaart Hospital, Amsterdam, The Netherlands
Search for more papers by this authorFrederik J. M. Slors
Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorHans F. A. Vasen
The Netherlands Foundation for the Detection of Hereditary Tumors, Leiden, The Netherlands
Search for more papers by this authorRiccardo Fodde
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands
Search for more papers by this authorAbstract
Familial adenomatous polyposis (FAP) is an inherited predisposition to colorectal cancer caused by germline mutations in the adenomatous polyposis coli (APC) gene located on chromosome segment 5q21-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; 10) (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. © 1995 Wiley-Liss, Inc.
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