Albanyan Saleh, Giles Rachel H, Gimeno Enric Mocholi, Silver Josh, Murphy Jillian, Faghfoury Hanna, Morel Chantal F, Machado Jerry, Kim Raymond H
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
Department of Nephrology and Hypertension, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, The Netherlands.
Eur J Med Genet. 2019 Mar;62(3):177-181. doi: 10.1016/j.ejmg.2018.07.006. Epub 2018 Jul 10.
Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome in which carriers are at an increased risk of developing a variety of tumors in multiple organ systems. A clinical diagnosis of VHL is determined by the presence of specific clinical manifestations while a molecular genetic diagnosis results from a pathogenic variant in the VHL gene. The majority of mutations occur in VHL coding exons and DNA analysis of these regions has a reported sensitivity of nearly 100%. However, rare variants in the VHL gene promoter may be detected in some cases of suspected VHL disease. We report two cases where VHL promoter variants were detected and describe the role of multi-step mRNA and protein analysis in the diagnostic evaluation of these cases.
冯·希佩尔-林道（VHL）病是一种遗传性肿瘤综合征，携带者在多个器官系统中发生多种肿瘤的风险增加。VHL的临床诊断取决于特定临床表现的存在，而分子遗传学诊断则源于VHL基因中的致病性变异。大多数突变发生在VHL编码外显子中，据报道对这些区域进行DNA分析的敏感性接近100%。然而，在一些疑似VHL病的病例中可能会检测到VHL基因启动子中的罕见变异。我们报告了两例检测到VHL启动子变异的病例，并描述了多步骤mRNA和蛋白质分析在这些病例诊断评估中的作用。
