title: SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma.
abstract: OBJECTIVE
  Hereditary head and neck paraganglioma (HNPGL) syndromes are associated with mutations in the SDHD(PGL1), SDHC(PGL3), and SDHB(PGL4) genes encoding succinate dehydrogenase subunits. We recently described mutations in a previously uncharacterized human gene, now called SDHAF2, and showed that this was the long-sought "imprinted" PGL2 gene. Here, we present a new branch of the Dutch SDHAF2 (PLG2-SDH5) family.
  
  
  METHODS
  The SDHAF2 family has been collected over a 30-year period. The family described here was linked to PGL2 and at-risk family members were invited to participate in this study. Patients were investigated and treated dependent on tumor size and localization. All family members have now been analyzed for the SDHAF2 mutation status.
  
  
  RESULTS
  Among the 57 family members, 23 were linkage positive including 7 risk-free carriers (maternal imprinting). Of the 16 at-risk individuals, 11 had a total of 24 tumors with primarily carotid (71%) and vagal locations (17%). Multifocality of tumors was prominent (91%). Malignancy was not detected. The average age at onset was 33 years, and many patients (42%) were asymptomatic prior to screening. SDHAF2 mutation analysis confirmed the findings of the previously performed linkage analysis without detection of discrepancies.
  
  
  CONCLUSIONS
  We established the SDHAF2 mutation status of PGL2 family members. Phenotypic characterization of this family confirms the currently exclusive association of SDHAF2 mutations with HNPGL. This SDHAF2 family branch shows a young age at onset and very high levels of multifocality. A high percentage of patients were asymptomatic at time of detection.
authors.affiliation: Department of Otorhinolaryngology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands. h.kunst@kno.umcn.nl
authors.forename: Henricus P M
authors.initials: HP
authors.lastname: Kunst
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Rutten
authors.forename: Jan-Pieter
authors.initials: JP
authors.lastname: de Mönnink
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Henri J L M
authors.initials: HJ
authors.lastname: Timmers
authors.forename: Henri A M
authors.initials: HA
authors.lastname: Marres
authors.forename: Jeroen C
authors.initials: JC
authors.lastname: Jansen
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bayley
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010235:Paraganglioma / Q000235:genetics*; D010375:Pedigree; D021122:Protein Subunits / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D021122:Protein Subunits; D013385:Succinate Dehydrogenase