Identification of a novel CNV at the APC gene in a Chinese family with familial adenomatous polyposis

Juyi Li; Chengzhi He; Jing Gong; Xiufang Wang; Chao Liu; Aiping Deng; Lin Zhu

doi:10.3389/fmolb.2023.1234296

Identification of a novel CNV at the APC gene in a Chinese family with familial adenomatous polyposis

Front Mol Biosci. 2023 Jul 27:10:1234296. doi: 10.3389/fmolb.2023.1234296. eCollection 2023.

Authors

Juyi Li¹, Chengzhi He², Jing Gong³, Xiufang Wang⁴, Chao Liu⁵, Aiping Deng¹, Lin Zhu⁶

Affiliations

¹ Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
² Department of Gastrointestinal Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
⁴ Department of Pain, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
⁵ Hubei Key Laboratory of Diabetes and Angiopathy, Hubei University of Science and Technology, Xianning, Hubei, China.
⁶ Department of Pediatrics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract

Introduction: Familial adenomatous polyposis (FAP) is the second most commonly inherited colorectal cancer (CRC) predisposition caused by germline mutations within the adenomatous polyposis coli (APC) gene. The molecular defects and clinical manifestations of two FAP families were analyzed, and individual prevention strategies suitable for mutation carriers in different families were proposed. Methods and results: The pathogenic gene mutations were identified among the two families using whole-exome sequencing and verified with Sanger sequencing or quantitative polymerase chain reaction (qPCR). One novel (GRCh37:Chr5: 112145676-112174368, del, 28,692 bp) and a known (c.C847T:p.R283X) mutation in the APC gene were pathogenic mutations for FAP, according to the sequencing data and tumorigenesis pattern among the family members. The two mutations led to a premature translational stop signal, synthesizing an absent or disrupted protein product. Conclusion: Our findings expand the known germline mutation spectrum of the APC gene among the Chinese population. This reaffirms the importance of genetic testing in FAP. Genetic consultation and regular follow-ups are necessary for the individualized treatment of cancer-afflicted families with APC expression deficiency. Additional work is required to develop safe and effective chemotherapy and immunotherapy for FAP based on the mutation type.

Keywords: adenomatous polyposis coli gene; copy number variations; familial adenomatous polyposis; genetic counseling; whole-exome sequencing.

Grants and funding

This study was supported by the Wuhan Municipal Health Commission (No. WX18M02), Central Guiding Local Science and Technology Development Special Project (No. 2022BGE272), and Guangdong Yiyang Healthcare Charity Foundation (JZ2022011).