Clinical characteristics and APC gene mutation spectrum of familial adenomatous polyposis patients in China

Purpose Given the limited clinical and molecular characterization of familial adenomatous polyposis (FAP) in Chinese populations, this study delineates the APC mutational landscape in national probands and correlates genotypic profiles with phenotypic manifestations. Methods Comprehensive APC gene sequencing was conducted in 33 unrelated Chinese polyposis patients, with subsequent genotype-phenotype correlation analysis leveraging clinical data from index cases and affected relatives. Results Germline APC mutations were identified in 28/33 (84.8%) probands. Patients with profuse FAP developed polyposis and cancer significantly earlier than attenuated or intermediate subtypes (p < 0.05). 13 out of 35 mutations (46.4%) were localized within exon 15. Codon 1309 has the highest mutation frequency(7%,2/29). 7 novel APC mutations were identified, including c.646-1 > T, c.1285delC, c.1350_1352delinsAC, c.3992_3993insA, c.230_233delTAGA, EX5_16DEL, Ex3_16DEL. Most intermediate FAP cases (92.9%, 13/14) had disease-causing mutations in codons 157–1595, matching the known mutation hotspot region. 100% (4/4) of congenital hypertrophy of retinal pigment epithelium, 75% (3/4) of gastroduodenal adenomas, and 50% (1/2) of desmoid tumor cases were localized to established APC risk domains. Conclusion Our comprehensive profiling of APC variants in Chinese polyposis patients delineated clinical characteristics and novel pathogenic mutations. Crucially, we observed divergent genotype-phenotype correlations in part of mutation-positive families, necessitating tailored genetic counseling and management strategies for this population.