title: Molecular genetic diagnosis of von Hippel-Lindau disease in familial phaeochromocytoma.
abstract: Inherited predisposition to phaeochromocytoma is seen in multiple endocrine neoplasia type 2 syndromes, von Hippel-Lindau (VHL) disease, and neuro-fibromatosis type 1. In addition familial phaeochromocytoma alone has been reported. To investigate the genetic basis for familial phaeochromocytoma alone, we screened three affected kindreds for mutations in the RET proto-oncogene and the VHL tumour suppressor gene. We did not detect MEN 2 associated RET mutations in any family, but missense VHL gene mutations (V155L and R238W) were identified in two kindreds with no clinical evidence of VHL disease. Patients with familial, multiple, or early onset phaeochromocytoma should be investigated for germline VHL and RET gene mutations as the molecular diagnosis of multisystem familial cancer syndromes enables appropriate counselling and screening to be provided.
authors.affiliation: Human Molecular Genetics Group, University of Cambridge, Department of Pathology, Addenbrooke's Hospital, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Crossey
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: M
authors.initials: M
authors.lastname: Ginalska-Malinowska
authors.forename: T W
authors.initials: TW
authors.lastname: Lennard
authors.forename: D C
authors.initials: DC
authors.lastname: Wheeler
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
authors.forename: E R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008025:Ligases; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics*; D017354:Point Mutation; D011506:Proteins / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000175:diagnosis / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D008025:Ligases; C497446:VHL protein, human