Genotype-phenotype correlation in Iranian retinal hemangioblastoma patients and genetic diagnosis algorithm for Von Hippel-Lindau disease.

Abstract

Analyzing Von Hippel-Lindau (VHL) variants and their correlation with phenotypes provides valuable insights into the genetic underpinnings of the disease. Among the most common mutations observed in these patients were missense (MS) mutations, followed by large deletions, and protein-truncating mutations (PTM). Notably, mutation sites in exon 3 (α domain) were more prevalent compared to other sites (65% vs. 35%). Splice site mutations were identified as high-risk mutations, while mutation c.467A>G was categorized as low-risk. After grouping the mutations into MS and Non-Missense (NMS) categories and analyzing mutation locations, statistical analysis revealed that RH patients with MS mutations had a 0.2 times lower likelihood of developing central nervous system hemangioblastoma (CHB) compared to those with NMS mutations. Additionally, the probability of MS mutations occurring in the superior, infratemporal, and temporal regions was 0.5 times lower than NMS mutations. For studying VHL mutations in the Iranian population, it is recommended to prioritize the examination of exon 3, followed by exon 1, and then exon 2.