APC and MUTYH analysis in FAP patients: A novel mutation in APC gene and genotype-phenotype correlation

APC and MUTYH genes are mutated in 70–90% and 10–30% of familial adenomatous polyposis cases (FAP) respectively. An association between mutation localization and FAP clinical phenotype is reported. The aims of this study were to determine APC and MUTYH mutational status in a small cohort of FAP patients and to evaluate the genotype-phenotype correlation in mutated patients. Here, we report the identification of a novel APC germline mutation, c.510_511insA. Overall, mutational analysis showed pathogenic mutations in 6/10 patients: 5/10 in APC and 1/10 in MUTYH. Additionally, we found three variants of unknown significance in MUTYH gene that showed no evidence of possible splicing defects by in silico analysis. Molecular analysis was also extended to family members of mutated patients. A genotype-phenotype correlation was observed for colonic signs whereas a variation of disease onset age was revealed for the same mutation. Moreover, we found an intrafamilial variability of FAP onset age. Regarding extracolonic manifestations, the development of desmoid tumors was related to surgery and not to mutation position, while a genotype-phenotype correspondence was observed for the onset of thyroid or gastric cancer. These findings can be useful in association to clinical data for early surveillance and suitable treatment of FAP patients