title: The von Hippel-Lindau (VHL) germline mutation V84L manifests as early-onset bilateral pheochromocytoma.
abstract: Von Hippel-Lindau (VHL) disease is a heritable tumor susceptibility syndrome caused by germline mutations in the VHL gene. The types of tumor that can occur in affected individuals include retinal and central nervous system hemangioblastoma, renal cell carcinoma, pheochromocytoma, and others. The pattern of tumor types that develops in a VHL-affected family defines the clinical subtype (1, 2A, 2B, 2C). Generally, it is difficult to accurately predict an individual's clinical phenotype based on their VHL mutation. However, in a few specific VHL mutations, a strong genotype-phenotype correlation has been established. We report here on the clinical findings in individuals from three unrelated families with a V84L VHL germline mutation, and present follow-up information regarding the only other reported family with this missense mutation. In each of these four families, the major clinical manifestation of VHL disease is multiple early-onset pheochromocytomas (VHL type 2C). This series of eight patients strengthens the correlation between the V84L mutation and the VHL type 2C phenotype, and improves our ability to provide prognostic and management recommendations for similarly affected individuals.
authors.affiliation: Division of Human Genetics, University of Connecticut Health Center, Farmington, Connecticut 06119, USA.
authors.forename: Mary-Alice
authors.initials: MA
authors.lastname: Abbott
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.forename: Simon
authors.initials: S
authors.lastname: Nightingale
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Robert M
authors.initials: RM
authors.lastname: Greenstein
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000209:etiology / Q000473:pathology*; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D010673:Pheochromocytoma / Q000209:etiology / Q000473:pathology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human