Catapano Domenico, Muscarella Lucia Anna, Guarnieri Vito, Zelante Leopoldo, D'Angelo Vincenzo Antonio, D'Agruma Leonardo
Casa Sollievo della Sofferenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy.
Neurosurgery. 2005 Jun;56(6):1215-21; discussion 1221. doi: 10.1227/01.neu.0000159646.15026.d6.
Hemangioblastomas of the central nervous system (CNS) are benign neoplasms that may occur sporadically or in association with von Hippel-Lindau (VHL) disease. The proportion of primary symptomatic hemangioblastomas associated with VHL disease is estimated to be from 10 to 40%, but it seems to be underestimated. We investigated the frequency of VHL germline mutation in patients with symptomatic CNS hemangioblastoma without evidence of VHL disease to define the role of molecular genetic analysis in the management of such patients and their relatives.
We analyzed 14 patients (6 female and 8 male; mean age, 43.5 yr) with no family history and no other clinical manifestations of VHL disease who had been operated on for symptomatic CNS hemangioblastoma. Exons 1, 2, and 3 of the VHL gene and their immediately flanking sequences were amplified by use of polymerase chain reaction followed by analysis with denaturing high-performance liquid chromatography and sequencing the anomalous samples.
Germline mutations of the VHL gene were identified in 2 (14%) of 14 patients. VHL gene mutation analysis was performed in both patients' family members, which showed another affected asymptomatic subject for VHL disease. The affected subjects were recommended for VHL disease surveillance protocol.
Molecular genetic analysis is a safer and more specific instrument to confirm or exclude VHL disease in patients with CNS hemangioblastoma, a negative family history, or absence of other known manifestations of the disease. Early identification of VHL mutation gene carriers is important for reducing disease morbidity and mortality. Nonsymptomatic family members will benefit from early VHL disease diagnosis or by being excluded as at-risk subjects, reducing the psychological and economic burden of screening and surveillance protocols.
中枢神经系统（CNS）血管母细胞瘤是一种良性肿瘤，可散发出现或与冯·希佩尔-林道（VHL）病相关。据估计，与VHL病相关的原发性有症状血管母细胞瘤的比例为10%至40%，但似乎被低估了。我们调查了有症状的CNS血管母细胞瘤患者中VHL基因种系突变的频率，这些患者无VHL病证据，以确定分子遗传学分析在此类患者及其亲属管理中的作用。
我们分析了14例无VHL病家族史且无其他临床表现、因有症状的CNS血管母细胞瘤接受手术治疗的患者（6例女性，8例男性；平均年龄43.5岁）。使用聚合酶链反应扩增VHL基因的第1、2和3外显子及其紧邻的侧翼序列，随后用变性高效液相色谱分析并对异常样本进行测序。
14例患者中有2例（14%）鉴定出VHL基因种系突变。对这2例患者的家庭成员均进行了VHL基因突变分析，结果显示另有1名无症状的VHL病患者。建议这些受影响的受试者接受VHL病监测方案。
分子遗传学分析是一种更安全、更特异的手段，可用于确认或排除无家族史或无其他已知疾病表现的CNS血管母细胞瘤患者是否患有VHL病。早期识别VHL突变基因携带者对于降低疾病发病率和死亡率很重要。无症状的家庭成员将受益于早期VHL病诊断或被排除为高危受试者，从而减轻筛查和监测方案的心理和经济负担。
