{"id":12677,"date":"2026-03-16T00:00:00","date_gmt":"2026-03-16T00:00:00","guid":{"rendered":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1776361"},"modified":"2026-03-16T00:00:00","modified_gmt":"2026-03-16T00:00:00","slug":"a-novel-pathogenic-apc-variant-identified-in-a-chinese-pedigree-with-familial-adenomatous-polyposis","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/03\/16\/a-novel-pathogenic-apc-variant-identified-in-a-chinese-pedigree-with-familial-adenomatous-polyposis\/","title":{"rendered":"A novel pathogenic APC variant identified in a Chinese pedigree with familial adenomatous polyposis"},"content":{"rendered":"BackgroundFamilial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder characterized by the development of numerous colorectal polyps and a high predisposition to colorectal cancer, primarily caused by germline variants in the APC gene. This study aimed to identify and functionally validate a novel APC variant in a Chinese FAP pedigree.MethodsA three-generation Chinese FAP pedigree was recruited. Peripheral blood samples were collected from family members to extract genomic DNA. Whole-exome sequencing (WES) was performed to screen candidate variants, and Sanger sequencing was used for verification. SW480 cells (endogenously deficient in functional APC) were divided into three groups: empty vector group, APC-wild-type (APC-WT) group, and APC-mutant group. Western blot analysis was conducted to detect \u03b2-catenin protein expression levels, to evaluate the functional impact of the identified variant.ResultsThe proband\u2019s FAP-associated colorectal cancer was identified as exhibiting microsatellite instability high (MSI-H) with a classic MLH1\/PMS2 dual loss pattern. A novel germline variant APC c.3799dup was identified in all affected family members but was absent in unaffected individuals. Western blot analysis showed that \u03b2-catenin protein levels in the APC-WT group were significantly lower than those in the APC-Mutant group (P < 0.05) and the empty vector group (P < 0.01). This indicated that the c.3799 dup variant abolished APC\u2019s ability to promote \u03b2-catenin degradation, leading to sustained activation of the Wnt\/\u03b2-catenin pathway.ConclusionThe novel APC variant c.3799 dup is a pathogenic variant associated with FAP. Our findings expand the spectrum of known APC variants and provide functional evidence for the pathogenicity of this variant. The rare co-occurrence of FAP and MSI-H in the proband enriches the molecular phenotypic spectrum of FAP-related tumors.","protected":false},"excerpt":{"rendered":"<p>BackgroundFamilial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder characterized by the development of numerous colorectal polyps and a high predisposition to colorectal cancer, primarily caused by germline variants in the APC gen&#8230;<\/p>\n","protected":false},"author":487,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,12,13,82],"tags":[71],"class_list":["post-12677","post","type-post","status-publish","format-standard","hentry","category-articulos","category-enfermedades-raras","category-frontiers-in-genetics","category-original-research","tag-frontgenet"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/12677","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/487"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=12677"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/12677\/revisions"}],"predecessor-version":[{"id":12678,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/12677\/revisions\/12678"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=12677"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=12677"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=12677"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}