title: Germline VHL gene mutations in Hungarian families with von Hippel-Lindau disease and patients with apparently sporadic unilateral pheochromocytomas.
abstract: OBJECTIVE
  Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome caused by mutations or deletions of the VHL tumor-suppressor gene. Germline VHL gene alterations may be also present in patients with apparently sporadic pheochromocytoma (ASP), although a wide variation in mutation frequencies has been reported in different patient cohorts.
  
  
  METHODS
  Herein, we report the analysis of the VHL gene in Hungarian families with VHL disease and in those with ASP.
  
  
  METHODS
  Seven families (35 members) with VHL disease and 37 unrelated patients with unilateral ASP were analyzed. Patients were clinically evaluated and the VHL gene was analyzed using direct sequencing, multiplex ligation-dependent probe amplification, and real-time PCR with SYBR Green chemistry.
  
  
  RESULTS
  Disease-causing genetic abnormalities were identified in each of the seven VHL families and in 3 out of the 37 patients with ASP (one nonsense and six missense mutations, two large gene deletions and one novel 2 bp deletion). Large gene deletions and other genetic alterations resulting in truncated VHL protein were found only in families with VHL type 1, whereas missense mutations were associated mainly, although not exclusively, with VHL type 2B and type 2C.
  
  
  CONCLUSIONS
  The spectrum of VHL gene abnormalities in the Hungarian population is similar to that observed in Western, Japanese, or Chinese VHL kindreds. The presence of VHL gene mutations in 3 out of the 37 patients with ASP suggests that genetic testing is useful not only in patients with VHL disease but also in those with ASP.
authors: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, 46 Szentkirályi Street, Budapest H-1088, Hungary.
authors: Peter
authors: P
authors: Gergics
authors: Attila
authors: A
authors: Patocs
authors: Miklos
authors: M
authors: Toth
authors: Peter
authors: P
authors: Igaz
authors: Nikolette
authors: N
authors: Szucs
authors: Istvan
authors: I
authors: Liko
authors: Ferenc
authors: F
authors: Fazakas
authors: Istvan
authors: I
authors: Szabo
authors: Balazs
authors: B
authors: Kovacs
authors: Edit
authors: E
authors: Glaz
authors: Karoly
authors: K
authors: Racz
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000235:genetics*; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D010673:Pheochromocytoma / Q000150:complications / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000235:genetics
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein