Clinical-alimentary tractGenetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis☆
Section snippets
Materials and methods
All aspects of this study were reviewed and approved by the Institutional Review Board of the University of Utah.
Mutation testing in kindreds
The entire kindred 353 included more than 4000 members spanning 7 generations. Our research efforts focused on 2 of 5 branches in which the APC mutation was transmitted. These branches were designated “B” and “E” and contained 1707 individuals. Kindred 439 contained 550 individuals. The specific AFAP mutation was present in 43 of 299 tested individuals from K353(B) and was absent in the remaining 256. One hundred four of 416 tested individuals from K353(E) carried the mutation, and 312 did not.
Discussion
The clinical characteristics of these 2 kindreds, in view of their size and genetic diagnosis, allow a highly precise definition of the colonic polyp and cancer risk of the syndrome of AFAP in the kindreds studied. The phenotype first seemed related to FAP when we found linkage in kindred 353 to the APC gene.1 Identification of the disease-causing mutation in the APC gene2 has subsequently allowed us to make precise genetic diagnoses of kindred members, accurate clarification of the phenotype,
Acknowledgements
The authors thank Stacey Maxwell and Mark Mayle for their efforts in recruiting and working with research participants, Jamie McDonald for providing genetic counseling, Melanie Nichols for coordinating and completing the mutation analysis, and Shannon Spilker for data abstraction.
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2022, Gastrointestinal Endoscopy Clinics of North AmericaCitation Excerpt :Given the proximal nature of polyps in AFAP, colonoscopy is recommended, at an interval of every 1 to 2 years. Prior studies suggest that endoscopic surveillance and polypectomy may delay or even prevent the need for surgery in individuals with AFAP and a manageable polyp burden.8,12,21 However, the same surgical indications for FAP apply to the AFAP phenotype as well.
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Supported by National Cancer Institute grants R01-CA40641 and PO1-CA73992; additional support was provided by Cancer Center Support grants P30-CA42014, M01-RR00064, and N01-PC-67000 and by the Huntsman Cancer Foundation.