Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA.
Urologic Oncology Branch, National Cancer Institue, Bethesda, Maryland, USA.
J Med Genet. 2022 Jan;59(1):18-22. doi: 10.1136/jmedgenet-2020-107308. Epub 2020 Oct 16.
Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary tumour susceptibility disease caused by germline pathogenic variation of the tumour suppressor gene. Affected individuals are at risk of developing multiple malignant and benign tumours in a number of organs.In this report, a male patient in his 20s who presented to the Urologic Oncology Branch at the National Cancer Institute with a clinical diagnosis of VHL was found to have multiple cerebellar haemangioblastomas, bilateral epididymal cysts, multiple pancreatic cysts, and multiple, bilateral renal tumours and cysts. The patient had no family history of VHL and was negative for germline mutation by standard genetic testing. Further genetic analysis demonstrated a germline balanced translocation between chromosomes 1 and 3, t(1;3)(p36.3;p25) with a breakpoint on chromosome 3 within the second intron of the gene. This created a pathogenic germline alteration in by a novel mechanism that was not detectable by standard genetic testing.Karyotype analysis is not commonly performed in existing genetic screening protocols for patients with VHL. Based on this case, protocols should be updated to include karyotype analysis in patients who are clinically diagnosed with VHL but demonstrate no detectable mutation by existing genetic testing.
希佩尔-林道（VHL）病是一种常染色体显性遗传肿瘤易感性疾病，由肿瘤抑制基因的种系致病性变异引起。受影响的个体有多个器官发生多种恶性和良性肿瘤的风险。在本报告中，一名 20 多岁的男性患者因 VHL 的临床诊断到国家癌症研究所泌尿科肿瘤学分会就诊，发现他患有多个小脑血管母细胞瘤、双侧附睾囊肿、多个胰腺囊肿、多个双侧肾肿瘤和囊肿。该患者无 VHL 的家族史，经标准遗传检测呈种系突变阴性。进一步的遗传分析显示 1 号和 3 号染色体之间存在种系平衡易位，t(1;3)(p36.3;p25)，3 号染色体上的断裂点位于 基因的第二个内含子内。这通过一种新的机制导致了 的致病性种系改变，而标准遗传检测无法检测到这种改变。核型分析在现有的 VHL 患者遗传筛查方案中并不常见。基于本病例，应更新方案，将核型分析纳入到临床诊断为 VHL 但现有遗传检测未发现可检测突变的患者中。
