To evaluate the Von Hippel-Lindau (VHL) related mutations in patients with RCH and their first-degree family members.

In this prospective observational case series, patients with RCH and their first-degree relatives were included based on VHL international criteria: -Negative family history for VHL syndrome: ≥2 retinal hemangioblastoma, ≥2 brain hemangioblastoma, Single retinal or brain hemangioblastoma with the visceral lesion. -Positive family history for VHL: Solitary Retinal, hemangioblastoma, Solitary Brain hemangioblastoma, visceral lesion. Family history about any death due to systemic manifestations of VHL-syndrome was asked from patients. To detect the mutations, evaluation of small nucleotide variant and Small Indell based on Sanger Sequencing was done. To detect the Copy Number Variant in patients with the negative mutation in the Sanger method, Multiple Ligand Probe Amplification (MLPA) was done.

Twenty-one families, (29 patients and 20 first-degree relatives) were studied. The mean age of the participants was 58.5 and 34 of them (69.3%) were female. We found the mutation in 12 (57.4%) families and in 14 (28.5%) participants. All the mutations were the heterozygote. Of them, 9 (64.3%) were point mutation and 5 (35.7%) were deletion mutation. Deletion mutations were on exon 1 (1 case), exon 2 (1 case) and exon 3 (2 cases).

Genetic study of the patients with RCH would help to detect the disease in earlier stages in first-degree relatives, and could be beneficial in the management of these patients.