title: Genetics of pheochromocytoma and paraganglioma in Spanish patients.
abstract: BACKGROUND
  The presence of familial history in pheochromocytoma/paraganglioma patients, including syndromic antecedents, leads in the majority of cases to a positive genetic testing for mutations in one of the major susceptibility genes described so far. Furthermore, it has been reported that in the absence of familial antecedents, about 11-24% of patients also carry a mutation in one of these related genes. In these cases, other clinical aspects like bilaterality, multiplicity, location of the tumors, or age at onset can help to recognize the underlying genes involved.
  
  
  OBJECTIVE
  The objective of the study was to discuss clinical criteria helpful in the genetic diagnosis, placing special emphasis on apparently sporadic cases.
  
  
  METHODS
  Two hundred thirty-seven nonrelated probands were analyzed for the major susceptibility genes: VHL, RET, SDHB, SDHC, and SDHD. Genetic characterization included both point mutation analysis and gross deletions in the SDH genes performed by multiplex PCR.
  
  
  RESULTS
  As expected, all syndromic probands were genetically diagnosed with a mutation affecting either RET or VHL. A total of 79.1% (19 of 24) and 18.4% (31 of 168) of patients presenting with either nonsyndromic familial antecedents or apparently sporadic presentation were found to carry a mutation in one of the susceptibility genes. Finally, we found a Spanish founder effect for two mutations: SDHB c.166_170delCCTCA and SDHD c.129G>A.
  
  
  CONCLUSIONS
  Germline mutations are rare in apparently sporadic probands diagnosed after age 40 yr (3.9% in our series) and mainly involve SDHB. Therefore, we recommend prioritizing SDHB genetic testing in patients developing isolated tumors at any age, especially those with extraadrenal location or malignant behavior.
authors.affiliation: Hereditary Endocrine Cancer Group, Institute de Salud Carlos III Center for Biomedical Research on Rare Diseases, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cascón
authors.forename: Guillermo
authors.initials: G
authors.lastname: Pita
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.forename: Iñigo
authors.initials: I
authors.lastname: Landa
authors.forename: Elena
authors.initials: E
authors.lastname: López-Jiménez
authors.forename: Cristina
authors.initials: C
authors.lastname: Montero-Conde
authors.forename: Susanna
authors.initials: S
authors.lastname: Leskelä
authors.forename: Luis Javier
authors.initials: LJ
authors.lastname: Leandro-García
authors.forename: Rocío
authors.initials: R
authors.lastname: Letón
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez-Antona
authors.forename: José Angel
authors.initials: JA
authors.lastname: Díaz
authors.forename: Emilio
authors.initials: E
authors.lastname: López-Vidriero
authors.forename: Anna
authors.initials: A
authors.lastname: González-Neira
authors.forename: Ana
authors.initials: A
authors.lastname: Velasco
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robledo
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D017668:Age of Onset; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000453:epidemiology / Q000235:genetics; D010235:Paraganglioma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D010673:Pheochromocytoma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D013030:Spain / Q000453:epidemiology; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000453:epidemiology / Q000235:genetics