title: TMEM127 screening in a large cohort of patients with pheochromocytoma and/or paraganglioma.
abstract: BACKGROUND
  TMEM127 is a novel pheochromocytoma (PCC) susceptibility gene.
  
  
  OBJECTIVE
  Our aim was to clearly determine the indications for TMEM127 genetic testing in patients with PCC and/or paraganglioma (PGL).
  
  
  METHODS
  Germline DNA from 642 unrelated patients who did not carry mutations in major PCC susceptibility genes was analyzed. Five hundred fifty-nine patients were affected by PCC, 72 by PGL (22 with head and neck and 50 with thoracic or abdominal location), and 11 by both PCC and PGL. Analysis of the TMEM127 gene was performed by direct sequencing and quantitative multiplex PCR of short fluorescent fragments.
  
  
  RESULTS
  In our cohort six mutations (0.9%) were identified. Three of them (p.Ala47Asp, p.Gln64HisfsX18, p.Tyr164X) were found in patients exhibiting clinical criteria for a hereditary disease (young age at diagnosis, bilateral PCC, or family history). The three others (p.Gln157X, p.Val68SerfsX13, p.Val90Met) were detected in patients with an apparently sporadic presentation. No mutation was found among patients with PGL, and no large chromosomal rearrangement spanning the TMEM127 gene was detected.
  
  
  CONCLUSIONS
  Our results combined with the two previous studies suggest that direct sequencing of TMEM127 should be considered, after a negative screening of VHL, RET, SDHB, and SDHD genes, in patients with PCC.
authors.affiliation: Département de Génétique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France.
authors.forename: Nassera
authors.initials: N
authors.lastname: Abermil
authors.forename: Marine
authors.initials: M
authors.lastname: Guillaud-Bataille
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.forename: Annabelle
authors.initials: A
authors.lastname: Venisse
authors.forename: Philippe
authors.initials: P
authors.lastname: Manivet
authors.forename: Laurence
authors.initials: L
authors.lastname: Guignat
authors.forename: Delphine
authors.initials: D
authors.lastname: Drui
authors.forename: Maurice
authors.initials: M
authors.lastname: Chupin
authors.forename: Claire
authors.initials: C
authors.lastname: Josseaume
authors.forename: Hélène
authors.initials: H
authors.lastname: Affres
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaître
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D008297:Male; D008403:Mass Screening; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C548370:TMEM127 protein, human