A novel missense mutation (N78D) in a family with von Hippel-Lindau disease with central nervous system haemangioblastomas, pancreatic and renal cysts

作者：Cingoz S; van der Luijt R B; Kurt E; Apaydin M; Akkol I; Ozgen Mihriban Heval^*

来源：Familial Cancer, 2013, 12(1): 111-117.

DOI：10.1007/s10689-012-9586-7

• VHL
• von Hippel-Lindau
• Pheochromocytoma
• Germline mutations
• Genotype-phenotype correlation

von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome caused by mutations in the VHL tumor suppressor gene. In a family with VHL, we identified a novel missense mutation (N78D), which affects a fully conserved residue in the VHL protein. Interestingly, several other missense mutations reported at same codon in the VHL protein that might be associated with a low risk of renal cell carcinoma (RCC) but not pheochromocytoma appear to be associated with a VHL type 1 phenotype. At the moment, RCC is present in none of the affected mutation carriers in the family described here. In contrast to other missense changes at codon 78, the change in our VHL family is predicted to have a mild effect on VHL function, which apparently is insufficient to cause predisposition to RCC. Our findings suggest that the risk of RCC in VHL is attributable to the severity of the amino acid substitution at this particular codon in the VHL protein.

• 出版日期2013-3