title: Mutations associated with succinate dehydrogenase D-related malignant paragangliomas.
abstract: OBJECTIVE
  Hereditary paraganglioma (PGL) syndromes result from germline mutations in genes encoding subunits B, C and D of the mitochondrial enzyme succinate dehydrogenase (SDHB, SDHC and SDHD). SDHB-related PGLs are known in particular for their high malignant potential. Recently, however, malignant PGLs were also reported among a small minority of Dutch carriers of the SDHD founder mutation D92Y. The aim of the study was to investigate which SDHD mutations are associated with malignant PGL.
  
  
  METHODS
  Case histories; collaborative study between referral centres in France, the USA, and the Netherlands.
  
  
  METHODS
  Six unrelated patients with metastatic PGLs of either sympathetic or parasympathetic origin.
  
  
  METHODS
  Assessment of SDHD mutations underlying malignant PGL.
  
  
  RESULTS
  Germline SDHD mutations underlying metastatic PGL were G148D, Y114X, L85X, W43X, D92Y, and IVS2+5G-->A.
  
  
  CONCLUSIONS
  Our findings indicate that malignant SDHD-related PGL is associated with several mutations besides D92Y.
authors.affiliation: Reproductive Biology and Adult Endocrinology Program, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1109, USA. h.timmers@endo.umcn.nl
authors.forename: Henri J L M
authors.initials: HJ
authors.lastname: Timmers
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
authors.forename: Michèle
authors.initials: M
authors.lastname: Duet
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: Patricia
authors.initials: P
authors.lastname: Niccoli-Sire
authors.forename: Ba Huy Patrice
authors.initials: BH
authors.lastname: Tran
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009423:Nervous System Neoplasms / Q000201:enzymology / Q000235:genetics*; D010235:Paraganglioma / Q000201:enzymology / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: C491545:SDHD protein, human; D013385:Succinate Dehydrogenase