国家神经系统疾病临床医学研究中心数据管理与共享系统
Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Clinical presentation and mutation analysis of VHL disease in a large Chinese family
通讯作者：Gui-Jun Jia
基本信息
- 负责人：Qing Zhang • De-Ling Li
- 数据来源： OTHERS
- 论文编号：OTHERS20190321
- 发表时间：2015-09-04
2015-09-04
已发表文章
主要研究背景及目的
方法
Systematic physical examinations, imaging assessments and molecular genetic tests for the VHL gene were performed in a large Chinese VHL family. The examined Chinese VHL family, which has 25 members from four generations, including 7 diagnosed VHL patients and 2 asymptomatic mutation carriers.
结论
We speculate that the p.Q145X nonsense mutation leads to relatively obvious familial aggregation. This mutation causes the type I phenotype of VHL disease and is associated with a high risk of retinal and central nervous system (CNS) hemangioblastomas (HGBs) and visceral cysts, but a low risk of renal cell carcinoma. Moreover, within a VHL family, the average ages of first onset became younger in successive generations, and the CNS HGBs are more likely to occur in male patients.
主要结果
The average ages of first onset for generations I, II, and III were 37, 30 and 16, respectively. The male:female ratio among VHL patients was 6:1. Molecular genetic investigations detected the c.433C>T [p.Q145X] nonsense mutation in the VHL gene. Molecular modeling of the VHL-ElonginC- ElonginB-HIF-1α complex predicted that the p.Q145X mutation markedly alters the L7 loop structure of the β-domain of the VHL protein (pVHL), destabilizes the VHL-HIF-1αcomplex, and induces the truncation of pVHL.