title: Mutations in SDHD are the major determinants of the clinical characteristics of Dutch head and neck paraganglioma patients.
abstract: OBJECTIVE
  Head and neck paragangliomas (HNPGL) are associated with mutations in genes encoding subunits of succinate dehydrogenase (SDH). The aim of this study was to evaluate SDH mutations, family history and phenotypes of patients with HNPGL in the Netherlands.
  
  
  METHODS
  We evaluated the clinical data and the mutation status of 236 patients referred between 1950 and 2009 to Leiden University Medical Center.
  
  
  RESULTS
  The large majority of the patients carried mutations in SDHD (83%), and the p.Asp92Tyr Dutch founder mutation in SDHD alone accounted for 72% of all patients with HNPGL. A mutation in SDHAF2 was found in 4%, mutations in SDHB in 3% and a mutation in SDHC was identified in a single patient (0·4%). Over 80% of patients presented with positive family history, of whom 99·5% carried a mutation in an SDH gene. SDH mutations were also found in 56% of isolated patients, chiefly in SDHD (46%), but also in SDHB (8%) and SDHC (2%). The clinical parameters of these different subgroups are discussed: including the age at diagnosis, associated pheochromocytomas, tumour multifocality and malignancy rate.
  
  
  CONCLUSIONS
  The majority of Dutch patients with HNPGL present with a positive family history, in contrast to other European countries. The clinical characteristics of patients with HNPGL are chiefly determined by founder mutations in SDHD, the major causative gene in both familial and isolated patients with HNPGL. The high frequency of founder mutations in SDHD suggests a higher absolute prevalence of paraganglioma syndrome in the Netherlands.
authors.affiliation: Department of Otolaryngology, Leiden University Medical Center, Leiden, the Netherlands. e.hensen@vumc.nl
authors.forename: E F
authors.initials: EF
authors.lastname: Hensen
authors.forename: M D
authors.initials: MD
authors.lastname: Siemers
authors.forename: J C
authors.initials: JC
authors.lastname: Jansen
authors.forename: E P M
authors.initials: EP
authors.lastname: Corssmit
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.forename: C M J
authors.initials: CM
authors.lastname: Tops
authors.forename: A G L
authors.initials: AG
authors.lastname: van der Mey
authors.forename: P
authors.initials: P
authors.lastname: Devilee
authors.forename: C J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: J P
authors.initials: JP
authors.lastname: Bayley
authors.forename: A H J T
authors.initials: AH
authors.lastname: Vriends
mesh_terms: D000328:Adult; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C108096:SDHC protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase