von Hippel-Lindau (VHL) 是一种常染色体显性遗传性肿瘤易感性疾病，与 VHL 肿瘤抑制基因的致病性种系变异相关。 VHL 患者发生多种良性和恶性肿瘤的风险增加。目前基于 CLIA 的基因检测表明，在具有 VHL 临床表现的患者中，种系 VHL 变异的检出率非常高。在本报告中，我们描述了一个具有典型 VHL 表现的大家族，常规种系测试未检测到该家族存在种系改变。我们在受影响的家庭成员中发现了一种涉及 3p 染色体的新型 291 kb 染色体倒位。这种倒位破坏了外显子 2 和外显子 3 之间的 VHL 基因，从而导致了该家族中观察到的疾病。© 作者（或其雇主）2024。根据 CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

von Hippel-Lindau (VHL) is an autosomal-dominant hereditary tumour susceptibility disease associated with pathogenic germline variants in the VHL tumour suppressor gene. VHL patients are at increased risk of developing multiple benign and malignant tumours. Current CLIA-based genetic tests demonstrate a very high detection rate of germline VHL variants in patients with clinical manifestations of VHL. In this report, we describe a large family with canonical VHL manifestations, for which no germline alteration had been detected by conventional germline testing. We identified a novel 291 kb chromosomal inversion involving chromosome 3p in affected family members. This inversion disrupts the VHL gene between exon 2 and exon 3 and is thereby responsible for the disease observed in this family.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.