Eye Research Center, the Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Stem cell and regenerative medicine research center, Iran University of Medical Sciences, Tehran, Iran.
Ophthalmic Genet. 2023 Jun;44(3):211-217. doi: 10.1080/13816810.2022.2138455. Epub 2023 Jan 30.
Retinal capillary hemangioblastoma (RCH), while sporadic in some cases, is the most common and earliest manifestation of von Hippel-Lindau disease (VHL). This is the first report on different types of VHL variants and genotype-phenotype correlations in Iranian families with RCH.
In this prospective observational case series study, 17 families with RCH were included. PCR was performed to amplify 3 exons of VHL gene. Afterward, Sanger sequencing was performed on all PCR products. For the detection of VHL copy number variations, MLPA was used.
Our study identified 10 different types of VHL variants. Missense mutations were the most common variants found and affected the structure of α domain of the VHL protein (pVHL). The majority of mutations (72.7%) in the patients with RCH and central nervous system hemangioblastoma (CNS-HB) were located on α domain.
α domain of VHL may play a potential role in the pathogenesis of RCH. Our findings suggest that genotype-phenotype characteristics in those variants in α- domain may predispose patients to RCH with CNS-HB.
视网膜毛细血管血管瘤（RCH）在某些情况下为散发性，但在 von Hippel-Lindau 病（VHL）中最为常见且最早出现。这是伊朗 RCH 家系中不同类型 VHL 变异体和基因型-表型相关性的首次报告。
在这项前瞻性观察性病例系列研究中，纳入了 17 个 RCH 家系。通过 PCR 扩增 VHL 基因的 3 个外显子，然后对所有 PCR 产物进行 Sanger 测序。为了检测 VHL 拷贝数变异，我们使用了 MLPA。
我们的研究鉴定出 10 种不同类型的 VHL 变异体。错义突变是最常见的变异体，影响 VHL 蛋白的α结构域（pVHL）。大多数（72.7%）在 RCH 和中枢神经系统血管母细胞瘤（CNS-HB）患者中发现的突变位于α结构域。
VHL 的α结构域可能在 RCH 的发病机制中发挥作用。我们的研究结果表明，那些位于α结构域的变异体的基因型-表型特征可能使患者易患伴有 CNS-HB 的 RCH。
