引言：家族性腺瘤性息肉病（FAP）是第二常见的遗传性结直肠癌（CRC）易感病，其原因是由腺瘤性息肉病大肠杆菌（APC）基因的生殖细胞突变所引起。本研究分析了两个FAP家族的分子缺陷和临床表现，并提出了适合不同家族突变携带者的个体预防策略。方法和结果：通过全外显子测序确定了这两个家族中的致病基因突变，并通过Sanger测序或定量聚合酶链反应（qPCR）进行了验证。APC基因中的一种新型（GRCh37：Chr5：112145676-112174368，del，28,692bp）和已知的一种（c.C847T：p.R283X）突变根据测序数据和家族成员的肿瘤发生模式，被确认为FAP的致病突变。这两种突变导致了翻译过程的过早终止信号，从而合成了缺失或破坏的蛋白质产物。结论：我们的发现扩展了中国人口中腺瘤性息肉病大肠杆菌（APC）基因的已知生殖细胞突变谱。这再次证实了FAP中基因测试的重要性。针对具有APC表达缺陷的患癌家族的个体化治疗，需要进行遗传咨询和定期随访。还需要进一步研究基于突变类型的FAP的安全有效的化疗和免疫疗法的开发。版权所有© 2023 Li、He、Gong、Wang、Liu、Deng和Zhu。

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.Copyright © 2023 Li, He, Gong, Wang, Liu, Deng and Zhu.