Ninety-eight individuals were tested for VHL mutations--23 symptomatic and 75 asymptomatic individuals belonging to 16 families. Seven of the families had definite clinical criteria of VHL disease, five had sporadic hemangioblastoma, and four had CNS hemangioblastoma combined with minor visceral signs. Molecular genetic testing identified five germline mutations in six of the definite VHL families (sensitivity 85%), but none in the possible VHL and sporadic hemangioblastoma cases; four of these mutations had been previously described and one is a novel mutation present in two unrelated families. After patients carrying the mutation were identified, they underwent clinical screening and asymptomatic VHL-related lesions were identified in 43%.
Patients presenting with cerebellar hemangioblastomas at the Mexican National institute of Neurology and Neurosurgery to were prospectively enrolled alongside family members, resulting in 84 patients in 7 families with VHL mutations, and subjected to peripheral blood draw and PCR-based mutation screening, as well as full clinical screening for symptomatic individuals. 19 individuals across two families (Family B and Family C) presented with a c.298dupA mutation, leading to a frameshift (p.T100Nfs 32). Among these individuals, 2 in Family B and 6 in Family C were asymptomatic at the time of screening (ages 2, 7, 9, 12, 13, 17, 20, and 29). Of the 4 symptomatic individuals in Family B, one presented at 44 with cerebellar hemangioblastoma and bilateral retinal angiomas; one presented at 16 with 4 cerebellar hemangioblastomas, 1 bulbar hemangioblastoma, 1 spinal hemangioblastoma, bilateral retinal angiomas, pancreatic cysts, and kidney cysts; one presented at age 26 with cerebellar hemangioblastoma, bilateral retinal angiomas, pancreatic cysts, kidney cysts, and renal cell carcinoma; and one presented at 28 with 1 cerebellar hemangioblastoma. Of the 7 symptomatic individuals in Family C, one presented at 45 with cerebellar hemangioblastoma, pancreatic cysts, kidney cysts, and renal cell carcinoma; one presented at age 21 with epididymal cystadenoma; one presented at 36 with 2 cerebellar hemangioblastomas, pancreatic cysts, kidney cysts, hepatic cysts, adrenal cysts, and bilateral renal cell carcinomas; one presented at 20 with spinal hemangioblastoma, pancreatic cysts, and kidney cysts; one presented at 13 with 2 spinal hemangioblastomas, one presented at 13 with cerebellar hemangioblastoma, one presented at 30 with cerebellar hemangioblastoma, pancreatic cysts, and kidney cysts. They were previously published in PMID: 20064270, however with a reportedly different variant: p.G34Rfs98 (c.99_100insA).