Danish Polyposis Register, Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Eur J Hum Genet. 2024 May;32(5):588-592. doi: 10.1038/s41431-024-01585-z. Epub 2024 Mar 12.
In the Danish Polyposis Register, patients with over 100 cumulative colorectal adenomas of unknown genetic etiology, named in this study colorectal polyposis (CP), is registered and treated as familial adenomatous polyposis (FAP). In this study, we performed genetic analyses, including whole genome sequencing (WGS), of all Danish patients registered with CP and estimated the detection rate of pathogenic variants (PV). We identified 231 families in the Polyposis Register, 31 of which had CP. A polyposis-associated gene panel was performed and, if negative, patients were offered WGS and screening for mosaicism in blood and/or adenomas. Next-generation sequencing (NGS) was carried out for 27 of the families (four declined). PVs were detected in 11 families, and WGS revealed three additional structural variants in APC. Mosaicism of a PV in APC was detected in two families. As the variant detection rate of eligible families was 60%, 93% of families in the register now have a known genetic etiology.
在丹麦息肉病登记处，登记并治疗了患有 100 个以上不明遗传病因的结直肠腺瘤的患者，这些患者在本研究中被命名为结直肠息肉病（CP），作为家族性腺瘤性息肉病（FAP）进行治疗。在这项研究中，我们对所有登记为 CP 的丹麦患者进行了包括全基因组测序（WGS）在内的遗传分析，并估计了致病性变异（PV）的检出率。我们在息肉病登记处发现了 231 个家族，其中 31 个家族患有 CP。进行了与息肉病相关的基因面板检测，如果结果为阴性，则为患者提供 WGS 检测以及血液和/或腺瘤中嵌合体的筛查。对 27 个家族（有四个家族拒绝）进行了下一代测序（NGS）。在 11 个家族中检测到了 PV，WGS 还揭示了 APC 中的另外三个结构变异。在两个家族中检测到 APC 中 PV 的嵌合体。由于合格家族的变异检测率为 60%，现在登记处的 93%的家族都有已知的遗传病因。
