A genetic register for von Hippel-Lindau disease
A genetic register for von Hippel-Lindau disease
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DOI：
10.1136/jmg.33.2.120
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发表时间：
1996-02-01
影响因子：
4
通讯作者：
Evans, DGR
中科院分区：
文献类型：
--
作者：
Maddock, IR;Moran, A;Evans, DGR
1990年，在英格兰西北部建立了冯·希佩尔-林道病的遗传登记处。研究了83例von Hippel-Lindau病（VHL）患者的人口统计学、临床特征、发病年龄和生存率。此外，还检查了筛查方案的有效性和一般人群中中枢神经系统血管母细胞瘤的发生率。西北地区杂合子的诊断点患病率为1.18/100 000（1/85 000）人，估计出生率为2.20/100 000（1/45 500）活产。直接估计突变率为1.4 × 10（-6）/基因/代（1/714200）。首次出现症状的平均年龄为26.25岁，小脑血管母细胞瘤是最常见的表现（34.9%的病例）。诊断VHL疾病的平均年龄为30.87岁。总共有50名患者（60.2%）发展为小脑血管母细胞瘤，34（41.0%）视网膜血管瘤，21例肾细胞癌25.3%，（14.5%）脊髓血管母细胞瘤，和12（14.5%）嗜铬细胞瘤。诊断肾细胞癌时的平均年龄年龄（38.9岁）明显高于小脑血管母细胞瘤（30.0岁）和视网膜血管瘤（21.1岁）。平均死亡年龄为40.9岁，小脑血管母细胞瘤是最常见的原因（47.7%的死亡）。共有65例VHL表现在适当的临床和放射学筛查试验后被诊断为无症状，尽管进行了适当的筛查，但只有两次未能检测到VHL疾病的表现。使用DNA连锁分析和直接突变检测将14人携带VHL基因的个人风险降低到1%以下。除了83例临床受影响的受试者外，还发现了3例尽管进行了广泛的筛查试验但仍被认为是病变fiee的专性携带者。在区域性癌症登记处发现的所有CNS血管母细胞瘤中，有14%是作为VHL疾病的一部分发生的，但对明显散发性疾病的VHL的调查似乎是有限的。
A genetic register for von Hippel-Lindau disease was set up in the north west of England in 1990. Population statistics, clinical features, age at onset, and survival of 83 people affected with von Hippel-Lindau (VHL) disease were studied. In addition, the effectiveness of the screening programme used and the occurrence of central nervous system haemangioblastomas in the general population were examined. The diagnostic point prevalence of heterozygotes in the North Western Region was 1.18/100 000 (1/85 000) people, with an estimated birth incidence of 2.20/100 000 (1/45 500) Live births. The mutation rate was estimated directly to be 1.4 x 10(-6)/gene/generation (1/714 200).The mean age at onset of first symptoms was 26.25 years, with cerebellar haemangioblastoma being the most common presenting manifestation (34.9% of cases). The mean age at diagnosis of VHL disease was 30.87 years. Overall, 50 patients (60.2%) developed a cerebellar haemangioblastoma, 34 (41.0%) a retinal angioma, 21 (25.3%) a renal cell carcinoma, 12 (14.5%) a spinal haemangioblastoma, and 12 (14.5%) a phaeochromocytoma.Mean age at diagnosis of renal cell carcinoma (38.9 years) was significantly higher than that for cerebellar haemangioblastoma (30.0 years) and retinal angioma (21.1 years). Mean age at death was 40.9 years with cerebellar haemangioblastoma being the most common cause (47.7% of deaths).A total of 65 VHL manifestations were diagnosed asymptomatically following appropriate clinical and radiological screening tests, and failure to detect manifestations of VHL disease in spite of appropriate screening occurred on only two occasions. The use of DNA linkage analysis and direct mutation testing reduced the personal risk of carrying the VHL gene to below 1% in 14 people. In addition to the 83 clinically affected subjects, three obligate carriers who were considered to be lesion fi ee in spite of extensive screening tests were identified.Fourteen percent of all CNS haemangioblastomas on the regionally based Cancer Registry were found to occur as part of VHL disease, but investigations for VHL in apparently sporadic disease appeared to be limited.