title: Paraganglioma and pheochromocytoma upon maternal transmission of SDHD mutations.
abstract: BACKGROUND
  The SDHD gene encodes a subunit of the mitochondrial tricarboxylic acid cycle enzyme and tumor suppressor, succinate dehydrogenase. Mutations in this gene show a remarkable pattern of parent-of-origin related tumorigenesis, with almost all SDHD-related cases of head and neck paragangliomas and pheochromocytomas attributable to paternally-transmitted mutations.
  
  
  METHODS
  Here we explore the underlying molecular basis of three cases of paraganglioma or pheochromocytoma that came to our attention due to apparent maternal transmission of an SDHD mutation. We used DNA analysis of family members to establish the mode of inheritance of each mutation. Genetic and immunohistochemical studies of available tumors were then carried out to confirm SDHD-related tumorigenesis.
  
  
  RESULTS
  We found convincing genetic and immunohistochemical evidence for the maternally-related occurrence of a case of pheochromocytoma, and suggestive evidence in a case of jugular paraganglioma. The third case appears to be a phenocopy, a sporadic paraganglioma in an SDHD mutation carrier with no immunohistochemical or DNA evidence to support a causal link between the mutation and the tumor. Microsatellite analysis in the tumor of patient 1 provided evidence for somatic recombination and loss of the paternal region of chromosome 11 including SDHD and the maternal chromosome including the centromere and the p arm.
  
  
  CONCLUSIONS
  Transmission of SDHD mutations via the maternal line can, in rare cases, result in tumorigenesis. Despite this finding, the overwhelming majority of carriers of maternally-transmitted mutations will remain tumor-free throughout life.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, PZ S-04, Leiden, 2300, RC, the Netherlands. j.p.l.bayley@lumc.nl.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bayley
authors.forename: Rogier A
authors.initials: RA
authors.lastname: Oldenburg
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nuk
authors.forename: Attje S
authors.initials: AS
authors.lastname: Hoekstra
authors.forename: Conny A
authors.initials: CA
authors.lastname: van der Meer
authors.forename: Esther
authors.initials: E
authors.lastname: Korpershoek
authors.forename: Barbara
authors.initials: B
authors.lastname: McGillivray
authors.forename: Eleonora P M
authors.initials: EP
authors.lastname: Corssmit
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.forename: Jeroen C
authors.initials: JC
authors.lastname: Jansen
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Hes
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D005260:Female; D050259:Genes, Mitochondrial; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000235:genetics* / Q000378:metabolism
chemical_list: C491545:SDHD protein, human; D013385:Succinate Dehydrogenase