Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China.
J Clin Neurosci. 2013 Jun;20(6):842-7. doi: 10.1016/j.jocn.2012.06.013. Epub 2013 Apr 28.
Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited familial cancer syndrome resulting from mutations in the VHL tumor suppressor gene, which leads to the development of a variety of benign and malignant tumors, especially central nervous system hemangioblastomas, retinal angiomas, clear-cell renal cell carcinomas and pheochromocytomas, with age-dependent penetrance. To date, nearly 400 germline mutations have been found to be involved in VHL disease according to the public Human Gene Mutation Database (HGMD). Although most index cases have a positive family history of VHL, some do not and may represent de novo cases. Patients diagnosed without family histories of VHL have been reported in as many as 23% of affected individuals with VHL. In this paper, we report the presence of a heterozygous deletion mutation of c.227_229delTCT in the VHL gene, causing the deletion of phenylalanine at codon 76 (p.Phe76del) of the VHL protein in a patient with sporadic VHL with a benign prognosis. The mutation involved may be de novo or the seemingly unaffected parent may be mosaic for the disease.
希佩尔-林道（VHL）病是一种常染色体显性遗传家族性癌症综合征，由 VHL 肿瘤抑制基因的突变引起，导致多种良性和恶性肿瘤的发生，特别是中枢神经系统血管母细胞瘤、视网膜血管瘤、肾透明细胞癌和嗜铬细胞瘤，具有年龄依赖性外显率。迄今为止，根据公共人类基因突变数据库（HGMD），已有近 400 种种系突变被发现与 VHL 病有关。尽管大多数索引病例具有 VHL 的阳性家族史，但有些没有，可能代表新生病例。在 VHL 患者中，有报道称多达 23%的患者无家族史。在本文中，我们报告了一名散发型 VHL 患者中 VHL 基因存在 c.227_229delTCT 杂合性缺失突变，导致 VHL 蛋白第 76 位密码子（p.Phe76del）的苯丙氨酸缺失。该突变可能是新生的，或者看似未受影响的父母可能是该病的嵌合体。
