Wong Wai T, Agrón Elvira, Coleman Hanna R, Reed George F, Csaky Karl, Peterson James, Glenn Gladys, Linehan W Marston, Albert Paul, Chew Emily Y
Division of Epidemiology and Clinical Research, Office of the Scientific Director, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Arch Ophthalmol. 2007 Feb;125(2):239-45. doi: 10.1001/archopht.125.2.239.
To characterize the germline mutations found in a large population of persons having von Hippel-Lindau (VHL) disease mutations with the clinical characteristics of associated retinal capillary hemangioblastomas (RCHs), to measure the prevalence of RCHs among patients with VHL disease generally and specifically for each genotype category, to establish genotype-phenotype correlations between genotype category and phenotypic features of ocular VHL disease, and to establish genotype-phenotype correlations between genotype category and visual function.
Cross-sectional and molecular genetic study. Of 890 patients with VHL disease, 335 had ocular involvement in the form of RCHs. Statistical analysis was used to correlate the structure of the mutated VHL protein with the ocular phenotype.
Three genotype categories (amino acid substitutions, protein-truncating mutations, and complete deletions of VHL protein) were defined in all patients. The prevalence of RCHs was lowest (14.5%) among patients with complete deletions; the overall prevalence of retinal angiomatosis was 37.2%. Genotype category had no correlation with the unilaterality or bilaterality of ocular disease or with the number or extent of peripheral RCHs. The prevalence of RCHs at the juxtapapillary location was lower among patients with protein-truncating mutations compared with those with amino acid substitutions. Complete deletions were associated with the highest mean visual acuity compared with the other 2 genotype categories.
Patients with complete deletions of VHL protein have the lowest prevalence of ocular disease and the most favorable visual outcome.
The VHL mutation genotype may be used to predict the prevalence and outcome of ocular VHL disease and to guide ophthalmic follow-up.
对大量携带冯·希佩尔－林道（VHL）病突变且伴有视网膜毛细血管瘤（RCH）临床特征的人群中发现的胚系突变进行特征分析，测量VHL病患者中RCH的总体患病率以及每种基因型类别的具体患病率，建立基因型类别与眼部VHL病表型特征之间的基因型-表型相关性，以及建立基因型类别与视觉功能之间的基因型-表型相关性。
横断面和分子遗传学研究。在890例VHL病患者中，335例有以RCH形式存在的眼部受累情况。采用统计分析将突变的VHL蛋白结构与眼部表型相关联。
在所有患者中确定了三种基因型类别（氨基酸替换、蛋白质截短突变和VHL蛋白完全缺失）。VHL蛋白完全缺失的患者中RCH的患病率最低（14.5%）；视网膜血管瘤病的总体患病率为37.2%。基因型类别与眼部疾病的单侧性或双侧性、周边RCH的数量或范围均无相关性。与氨基酸替换的患者相比，蛋白质截短突变的患者视乳头旁位置RCH的患病率较低。与其他两种基因型类别相比，VHL蛋白完全缺失与最高的平均视力相关。
VHL蛋白完全缺失的患者眼部疾病患病率最低，视觉预后最有利。
VHL突变基因型可用于预测眼部VHL病的患病率和预后，并指导眼科随访。
