AUTHOR=Li Juyi , He Chengzhi , Gong Jing , Wang Xiufang , Liu Chao , Deng Aiping , Zhu Lin 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1234296

DOI=10.3389/fmolb.2023.1234296

ISSN=2296-889X

ABSTRACT=<p><bold>Introduction:</bold> Familial adenomatous polyposis (FAP) is the second most commonly inherited colorectal cancer (CRC) predisposition caused by germline mutations within the <italic>adenomatous polyposis coli</italic> (<italic>APC</italic>) 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.</p><p><bold>Methods and results</bold>: 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 <italic>APC</italic> 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.</p><p><bold>Conclusion</bold>: Our findings expand the known germline mutation spectrum of the <italic>APC</italic> 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.</p>