RESUMO
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.