A deletion mutation of the VHL gene associated with a patient with sporadic von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited familial cancer syndrome resulting from mutations in the VHL tumor suppressor gene, which leads to the development of a variety of benign and malignant tumors, especially central nervous system hemangioblastomas, retinal angiomas, clear-cell renal cell carcinomas and pheochromocytomas, with age-dependent penetrance. To date, nearly 400 germline mutations have been found to be involved in VHL disease according to the public Human Gene Mutation Database (HGMD). Although most index cases have a positive family history of VHL, some do not and may represent de novo cases. Patients diagnosed without family histories of VHL have been reported in as many as 23% of affected individuals with VHL. In this paper, we report the presence of a heterozygous deletion mutation of c.227_229delTCT in the VHL gene, causing the deletion of phenylalanine at codon 76 (p.Phe76del) of the VHL protein in a patient with sporadic VHL with a benign prognosis. The mutation involved may be de novo or the seemingly unaffected parent may be mosaic for the disease.