title: A new germline VHL gene mutation in three patients with apparently sporadic pheochromocytoma.
abstract: BACKGROUND
  Germline mutations in four genes (RET, VHL, SDHB and SDHD) are detected in about 17% of patients with apparently sporadic pheochromocytoma. Thus, genetic screening of all patients with this disease is suggested for a rational diagnostic approach and management.
  
  
  OBJECTIVE
  To report the clinical, biochemical and genetic analysis of three unrelated patients affected by pheochromocytoma.
  
  
  METHODS
  All the coding regions and exon-intron boundaries of RET, VHL, SDHB and SDHD genes were sequenced in three unrelated patients with intra-adrenal pheochromocytoma: a 17-year-old girl, a 15-year-old boy and a 73-year-old man. The family history of all three cases was negative for von Hippel-Lindau lesions or other types of endocrine tumours. Structural modelling of the VHL protein was then performed.
  
  
  RESULTS
  We identified a novel germline VHL gene point mutation, a G to A nucleotide substitution in exon 3, leading to an aspartate to asparagine amino acid change in codon 197 (D197N). No mutations were found in RET, SDHB and SDHD genes. Structural modelling of the VHL protein suggests that the D197N mutation could have a functional role.
  
  
  CONCLUSIONS
  Our study expands the number of VHL gene known mutations and indicates the usefulness of performing the genetic analysis in all patients with apparently sporadic pheochromocytoma.
authors.affiliation: Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria, Udine, Italy.
authors.forename: Angela V
authors.initials: AV
authors.lastname: D'Elia
authors.forename: Franco
authors.initials: F
authors.lastname: Grimaldi
authors.forename: Stefano
authors.initials: S
authors.lastname: Pizzolitto
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Maglio
authors.forename: Elisa
authors.initials: E
authors.lastname: Bregant
authors.forename: Nadia
authors.initials: N
authors.lastname: Passon
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franzoni
authors.forename: Antonella
authors.initials: A
authors.lastname: Verrienti
authors.forename: Giulia
authors.initials: G
authors.lastname: Tamburrano
authors.forename: Cosimo
authors.initials: C
authors.lastname: Durante
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000368:Aged; D000595:Amino Acid Sequence; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010673:Pheochromocytoma / Q000235:genetics*; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human