title: High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas.
abstract: BACKGROUND
  Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments.
  
  
  METHODS
  We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age.
  
  
  RESULTS
  Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas.
  
  
  CONCLUSIONS
  Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.
authors.affiliation: Department of Endocrinology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart-Tilman, University of Liège, 4000 Liège, Belgium.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Tichomirowa
authors.forename: Anne
authors.initials: A
authors.lastname: Barlier
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Daly
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Jaffrain-Rea
authors.forename: Cristina
authors.initials: C
authors.lastname: Ronchi
authors.forename: Maria
authors.initials: M
authors.lastname: Yaneva
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Urban
authors.forename: Patrick
authors.initials: P
authors.lastname: Petrossians
authors.forename: Atanaska
authors.initials: A
authors.lastname: Elenkova
authors.forename: Antoine
authors.initials: A
authors.lastname: Tabarin
authors.forename: Rachel
authors.initials: R
authors.lastname: Desailloud
authors.forename: Dominique
authors.initials: D
authors.lastname: Maiter
authors.forename: Thomas
authors.initials: T
authors.lastname: Schürmeyer
authors.forename: Renato
authors.initials: R
authors.lastname: Cozzi
authors.forename: Marily
authors.initials: M
authors.lastname: Theodoropoulou
authors.forename: Caroline
authors.initials: C
authors.lastname: Sievers
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bernabeu
authors.forename: Luciana A
authors.initials: LA
authors.lastname: Naves
authors.forename: Olivier
authors.initials: O
authors.lastname: Chabre
authors.forename: Carmen Fajardo
authors.initials: CF
authors.lastname: Montañana
authors.forename: Vaclav
authors.initials: V
authors.lastname: Hana
authors.forename: Georges
authors.initials: G
authors.lastname: Halaby
authors.forename: Brigitte
authors.initials: B
authors.lastname: Delemer
authors.forename: José Ignacio Labarta
authors.initials: JI
authors.lastname: Aizpún
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Sonnet
authors.forename: Angel Ferrandez
authors.initials: AF
authors.lastname: Longás
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Hagelstein
authors.forename: Philippe
authors.initials: P
authors.lastname: Caron
authors.forename: Günter K
authors.initials: GK
authors.lastname: Stalla
authors.forename: Vincent
authors.initials: V
authors.lastname: Bours
authors.forename: Sabina
authors.initials: S
authors.lastname: Zacharieva
authors.forename: Anna
authors.initials: A
authors.lastname: Spada
authors.forename: Thierry
authors.initials: T
authors.lastname: Brue
authors.forename: Albert
authors.initials: A
authors.lastname: Beckers
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D004247:DNA