Pathogenic APC Variants in Latvian Familial Adenomatous Polyposis Patients

Abstract

Background and objectives: Familial adenomatous polyposis is one of the APC-associated polyposis conditions described as genetically predetermined colorectal polyposis syndrome with a variety of symptoms. The purpose of this study was to determine sequence variants of the APC gene in patients with familial adenomatous polyposis (FAP) phenotype and positive or negative family history. Materials and Methods: Eight families with defined criteria of adenomatous polyposis underwent molecular genetic testing. Coding regions and flanking intron regions of the APC gene were analyzed by Sanger sequencing. Results: Eight allelic variants of the APC gene coding sequence were detected. All allelic variants of the APC gene were predicted to be pathogenic based on criteria according to the "Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology" (2015), four of them c.1586_1587insAT, c.2336delT, c.3066_3067insGA, and c.4303_4304insC, were considered novel. Conclusions: The timely molecular genetic analysis of APC germline variants and standardized interpretation of the pathogenicity of novel allelic variants has a high impact on choice for treatment, cancer prevention, and family genetic counseling.

Keywords: APC gene; CRC; FAP; germline variants; pathogenic variants.

Figure 1

Medical history of cancers in the patients’ families. Abbreviations: CRC—colorectal cancer; Ut—cancer; C Su—cancer site unknown; Li – liver cancer; BR – breast cancer; Phar – pharyngeal cancer; Bl – bladder cancer; d – died.

Figure 2

APC germline variants identified by exon and codon location. The color bars represent genotype–phenotype correlation described earlier [19,20].