In addition to classic germline APC gene variants, APC mosaicism and deep intronic germline APC variants have also been reported to be causes of adenomatous polyposis. In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronic APC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detect APC mosaicism, we performed next-generation sequencing (NGS) in leukocyte DNA. Furthermore, using Sanger sequencing, the cohort was screened for the following previously reported deep intronic pathogenic germline APC variants: c.1408 + 731C > T, p.(Gly471Serfs*55), c.1408 + 735A > T, p.(Gly471Serfs*55), c.1408 + 729A > G, p.(Gly471Serfs*55) and c.532-941G > A, p.(Phe178Argfs*22). We did not detect mosaic or intronic APC variants in the screened unexplained colorectal polyposis patients. The results of this study indicate that the deep intronic APC variants investigated in this study are not a cause of colorectal polyposis in this Dutch population. In addition, NGS did not detect any further mosaic variants in our cohort.

除了经典的种系APC基因变异外，APC嵌合体和深内含子种系APC变异也被报道是腺瘤性息肉病的原因。在这项研究中，我们调查了 80 名原因不明的结直肠息肉病患者，这些患者在已知息肉易感基因中没有种系致病变异，以检测镶嵌和深内含子APC变异。所有患者均出现 50 多个结直肠息肉，主要观察到腺瘤。为了检测APC嵌合体，我们对白细胞 DNA 进行了新一代测序 (NGS)。此外，使用 Sanger 测序，对队列筛选以下先前报道的深内含子致病性种系APC变体：c.1408 + 731C > T, p.(Gly471Serfs*55), c.1408 + 735A > T, p.(Gly471Serfs*55), c.1408 + 729A > G, p.(Gly471Serfs*55) 和c.532-941G > A, p.(Phe178Argfs*22)。我们没有在筛查的原因不明的结直肠息肉病患者中检测到镶嵌或内含APC变异。本研究的结果表明，本研究中研究的深部内含子APC变异不是该荷兰人群结直肠息肉病的原因。此外，NGS 在我们的队列中没有检测到任何进一步的镶嵌变异。