# Phenotypic and Genotypic Features of a Chinese Cohort with Retinal Hemangioblastoma

## TL;DR

This study examines the genetic and clinical features of retinal hemangioblastoma in a Chinese population, finding that VHL-associated cases tend to appear earlier and have high rates of CNS tumors.

## Contribution

The study identifies novel VHL gene variants and highlights a notably high frequency of large genomic deletions in Chinese patients with VHL-associated retinal hemangioblastoma.

## Key findings

- VHL-associated retinal hemangioblastoma (RH) occurs earlier than non-VHL RH in Chinese patients.
- Large genomic deletions in the VHL gene were observed in 17.65% of cases.
- CNS hemangioblastomas were found in 80.65% of families with VHL-associated RH.

## Abstract

Purpose: To delineate the genotype and phenotype of RH in a Chinese cohort. Methods: A group of 51 Chinese probands with RH across 76 eyes was assembled and underwent complete retinal imaging examinations. Sanger sequencing and universal primer quantitative fluorescent multiplex–polymerase chain reaction (UPQFM-PCR) were employed for mutation detection in the coding region of the Von Hippel–Lindal (VHL) gene. For frequency calculation, our series was combined with three large cohorts of East Asian descent through a literature review. Results: The Von Hippel–Lindal (VHL) syndrome was excluded in fifteen patients (median age: 32.00 years) with unilateral solitary RH. Thirty-six patients of younger ages (median: 22.00 years, p = 0.008, Mann–Whitney test) conformed to the diagnostic criteria of the VHL syndrome, and thirty-four patients were genetically confirmed. There were four novel variants identified in the VHL gene. Codons 167, 161 and 86 exhibited a mutation occurrence of more than 5% after pooling with literature data, and the large genomic deletion demonstrated a frequency of 17.65%. The RHs were classified as “extrapapillary”, “juxtapapillary” and “mixed” types in 53, 7 and 5 eyes, respectively. Almost all extrapapillary RH lesions were found in the peripheral retina. Hemangioblastomas in the central nervous system (CNS) were observed in 25 out of 31 kindreds (80.65%) with full systemic evaluation data. Conclusions: VHL-associated RH might exhibit earlier onset than non-VHL RH. Large genomic deletions were observed at a notably high frequency in the Chinese series with VHL-associated RH, which might be associated with East Asian ethnicity background. RH could potentially serve as an early indicator of CNS hemangioblastoma.