Thirty-five unrelated patients suspected of having von Hippel-Lindau disease were analyzed and 32 VHL gene variants were found in 35 patients using PCR and SSCP by peripheral blood leukocytes. An association of clear cell renal carcinoma development with a relatively high loss of structural stability in VHL protein missense mutations was discovered. This nonsense mutation was found in a patient with retinal hemangioblastoma, cerebellar hemangioblastoma, and pancreatic cysts (patient no. F3). Patient has family history of paragangliomas, epididymial cysts, and clear cell renal carcinoma. Paper gives variant by protein sequence: L135*. NM_000551.3:c.404T>A and NM_000551.3:c.404T>G both could result in this protein change. Unclear which is correct to the given patient.

A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were included for analysis. This familial mutation was confirmed in family #48. Only the male proband (patient 128) was genetically confirmed with the mutation. He was diagnosed with CNS hemangioblastoma at 32Y, RCC at 38Y, pheochromocytoma at 40Y and multiple pancreatic lesions at 38Y. His father (patient 129) was diagnosed with RCC at 58Y and his daughter (patient 130) was diagnosed with CNS hemangioblastoma at 13Y. This cohort was also published in a paper by Wang et al., 2018 (PMID: 29330336).