World journal of gastroenterology · 2026
Genetic differences in familial adenomatous polyposis syndrome in a Hungarian population: A prospective single center study.
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Tóth Tibor, Bor Renáta, Nagy Dóra, Török Dóra, Molnár Tamás, Farkas Klaudia, Fábián Anna, Bősze Zsófia, Bálint Anita, Bacsur Péter, Resál Tamás, Szell Marta, Szepes Zoltán
Аннотация
BACKGROUND: Familial adenomatous polyposis (FAP) is a disorder of autosomal dominant inheritance that is responsible for around 1% of colorectal cancer (CRC) cases.
AIM: To determine the mutation profile of FAP-specific to the Hungarian population.
METHODS: This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP (aFAP). Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes. To identify larger deletions and insertions, a multiplex amplifiable probe hybridization technique was used. The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.
RESULTS: A total of 26 index patients with clinically suspected FAP (n = 21) and aFAP (n = 5) were enrolled. APC gene alterations were confirmed in 92.31% of the cases (region 1B deletion, n = 2; whole-gene deletion, n = 4; frameshift mutation, n = 2; nonsense mutation, n = 5, and splice mutation, n = 1), with the remaining two cases having CHEK2 and MSH3 gene alterations. According to pathogenicity, 21 cases had pathogenic mutations, 6 cases had likely pathogenic mutations, and 16 cases had variants of unknown significance (VUS). The most frequent of the latter were the POLE (n = 5) and PIEZO1 (n = 4) gene variants.
CONCLUSION: Germline mutations in the APC gene were confirmed in more than 90% of Hungarian patients with clinically suspected FAP. Although the role of VUS genes is unclear, they are highly likely to play a role in the development of CRC.
AIM: To determine the mutation profile of FAP-specific to the Hungarian population.
METHODS: This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP (aFAP). Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes. To identify larger deletions and insertions, a multiplex amplifiable probe hybridization technique was used. The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.
RESULTS: A total of 26 index patients with clinically suspected FAP (n = 21) and aFAP (n = 5) were enrolled. APC gene alterations were confirmed in 92.31% of the cases (region 1B deletion, n = 2; whole-gene deletion, n = 4; frameshift mutation, n = 2; nonsense mutation, n = 5, and splice mutation, n = 1), with the remaining two cases having CHEK2 and MSH3 gene alterations. According to pathogenicity, 21 cases had pathogenic mutations, 6 cases had likely pathogenic mutations, and 16 cases had variants of unknown significance (VUS). The most frequent of the latter were the POLE (n = 5) and PIEZO1 (n = 4) gene variants.
CONCLUSION: Germline mutations in the APC gene were confirmed in more than 90% of Hungarian patients with clinically suspected FAP. Although the role of VUS genes is unclear, they are highly likely to play a role in the development of CRC.