An update of the variant spectrum of the APC gene in Iranian familial adenomatous polyposis patients

Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominant colorectal cancer syndrome that is characterized by the development of multiple adenomas in the colon and rectum with high penetrance rates. This disease has specific features like the occurrence of pathogenic variations in the APC gene and diverse FAP phenotypes due to the occurrence region. In this study we aimed to evaluate pathogenic variants in exons of the APC gene in Iranian patients with FAP. A total of 35 FAP individuals were referred to the gastroenterology ward of Taleghani Hospital. As the aim of the study was to study the germline variations in the participants, the peripheral blood was collected and after the DNA extraction, PCR, and Sanger sequencing processes for the APC gene, the results were evaluated by the ACMG classification guidelines to report their pathogenicity. Accordingly, out of eight specific detected variants, three of them were novel, and the rest were reported previously. These eight variants were all truncating protein and pathogenic, and they were limited to 849–1378 codons. Overall, detected variants revealed discrepancies and parallels with previous reported cases in terms of quantity, occurrence region, and association with demographic and clinicopathological characteristics of patients. The spectrum of detected variants and the patient’s phenotype showed distinct characteristics, such as occurrence in specific regions and the absence of extracolonic symptoms like Congenital hypertrophy of the retinal pigment epithelium (CHRPE). These findings open the path to comprehending the typical symptoms, their rarity, and their occurrence in the Iranian population and also due to the facts, we found that the studying of the APC gene alone for diagnosing FAP disease is not sufficient, and considering other genes are completely rational in the case of sequencing and studying the variants.

Keywords:

• Pathogenic variants
• APC
• FAP
• coding regions

Acknowledgments

The authors would like to thank all the staff of the Cancer Department in the Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Ethical approval

This study was approved by the ethical committee (APPROVAL NUMBER: IR.SBMU.RIGLD.REC.1396.947) of the Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Consent to participate Informed consent was obtained from all subjects involved in the study.

Author contributions

Conceptualization, S.M.M., L.R., and E.N.M.; data curation, M.Y.T., and E.N.M.; formal analysis, S.M.M., and M.H.K., funding acquisition, M.R.Z.; investigation, P.L., E.N.M.; methodology, M.Y.T., M.G.; project administration, E.N.M, A.S.; resources, H.A.A.; software, H.S., N.F.; supervision, E.N.M.; validation, H.S. and P.K.; Lab working, M.Y.T., M.G., and S.M.M; writing—original draft, S.M.M., L.R., F.B.F. and E.N.M.; writing—review and editing, SM.M., N.F., L.R., P.K., F.B.F., and E.N.M. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

All new APC germline pathogenic variants have been submitted to LOVD database.

Additional information

Funding

This project was completely supported and funded by the Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, with Grant No. 858.