Mutation screening of VHL gene in a family with malignant bilateral pheochromocytoma: from isolated familial pheochromocytoma to von Hippel-Lindau disease

von Hippel-Lindau (vHL) disease is an inherited, autosomal dominant syndrome manifested by a variety of benign and malignant tumors. More than 300 germline VHL mutations have been identified that are involved in VHL disease. A large family (four generations) was evaluated. In this paper we report the presence of a single nucleotide mutation in exon 3 of VHL gene c499 C>T causing substitution of Arginine by Tryptophan at position 167 (R 167 W). It was detected in a family with bilateral malignant pheochromocytoma who has been followed for at least 9 years as RET negative isolated familial pheochromocytoma, finally diagnosed as von Hipple-Lindau disease according to retinal angioma and VHL gene mutation. VHL type 2 presenting with both pheochromocytoma and retinal angioma in this family found to be associated with the new missense mutation (c499 C>T) of VHL gene.