CLINICAL CHARACTERIZATION AND MUTATION SPECTRUM IN CRETAN PATIENTS WITH HEREDITARY POLYPOSIS SYNDROMES

Aims Hereditary polyposis syndromes are associated with an increased risk of colorectal cancer (CRC). Adenomatous polyps are present in familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP) and NTHL1-associated syndrome. Hamartomatous polyps are developed in Peutz-Jeghers and juvenile polyposis syndrome. The aim of this study was to investigate the phenotype and mutation spectrum of these syndromes among Cretan population.

Methods All Cretan patients who underwent colonoscopy at Venizeleio General Hospital between 1998 and 2021 with a diagnosis of≥10 adenomas or≥2 Peutz – Jeghers polyps or≥5 juvenile polyps were retrospectively reviewed. Genetic testing included a next-generation sequencing gene panel (HerediGENE^​).

Results Overall, 70 apparently unrelated probands were analyzed. Genetic testing revealed 5 APC mutations (c.730_731delAG, c.4653_4656delAGAG, Q1045X, c.3829delT, c.847C>T), 4 MUTYH mutations in 5 probands (c.1012C>T, c.1187G>A, c.734G>A, c.1227_1228dup), one NTHL1 mutation in 2 probands (c.268C>T), one BMPR1A (c.68-2A>G) and one STK11 mutation (c842_843insC). MAP was diagnosed during screening colonoscopy in 60% of MAP patients (3/5) while 2/5 were diagnosed with CRC, both of whom carriers of the c.1012C>T variant. Two probands carrying the NTHL1 c.268C>T variant were diagnosed with>50 colonic adenomas and one was diagnosed with CRC twice at ages 31 and 65.

Conclusions The genetic investigation of Cretan population revealed that every FAP family tested carried a different mutation. MUTYH mutation carriers presented variations in phenotype while the c.1012C>T variant was associated with a more severe phenotype. NTHL1 mutations resembled APC- and MUTYH-associated polyposis, in terms of polyp number present at diagnosis.

Publication History

Article published online:
14 April 2022