Clinical Characterization and Mutation Spectrum in Patients with Familial Adenomatous Polyposis in China.

BACKGROUND AND AIM: Familial adenomatous polyposis (FAP) is the most common adenomatous polyposis syndrome. Patients with FAP are screened for germline mutations of two genes, APC and MUTYH. However, limited data exists on the clinical characterization and genotypic spectrum of FAP in China. This study was aimed to determine APC and MUTYH mutational status in a small cohort of FAP probands in China and to characterize the genotype-phenotype correlation in mutated patients.

METHODS: Mutation screening of 46 unrelated probands was performed using multigene panels by next-generation sequencing (NGS). Clinical data of the index was used to assess genotype-phenotype correlations.

RESULTS: Overall, 42 out of 46 (91.30%) unrelated probands found mutations, including 35 (76.09%) with APC mutations, 3 (6.52%) with MUTYH mutations and 4 (8.70%) with both APC and MUTYH mutations. 10 APC genetic alterations variants were novel. The hereditary pattern of the family with both APC and MUTYH mutations was autosomal dominant inheritance. Upper gastrointestinal polyp was the most common extracolonic manifestations. The onset time for patients with both APC and MUTYH-mutation was earlier than MUTYH-mutation carriers, and similar to APC-mutation carriers. But the age of carcinogenesis for patients with both APC and MUTYH mutations was later than APC-mutation carriers and similar to MUTYH-mutation carriers.

CONCLUSION: In this study, we show the importance of using multigene panels which allows for a parallel comprehensive screening. We suggest that genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analysis simultaneously.