title: Frequency of AIP gene mutations in young patients with acromegaly: a registry-based study.
abstract: BACKGROUND
  Familial and sporadic GH-secreting pituitary adenomas are associated with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Patients with an AIP mutation (AIPmut) tend to have more aggressive tumors occurring at a younger age.
  
  
  OBJECTIVE
  The objective of the study was to investigate the frequency of AIPmut in patients diagnosed at 30 years of age or younger.
  
  
  METHODS
  The German Acromegaly Registry database (1795 patients in 58 centers) was screened for patients diagnosed with acromegaly at 30 years of age or younger (329 patients). Sixteen centers participated and 91 patients consented to AIPmut analysis.
  
  
  METHODS
  DNA was analyzed by direct sequencing and multiplex ligation dependent probe amplification Main outcome Measures: The number of patients with AIPmut was measured.
  
  
  RESULTS
  Five patients had either a mutation (c.490C>T, c.844C>T, and c.911G>A, three males) or gross deletions of exons 1 and 2 of the AIP gene (n = 2, one female). The overall frequency of an AIPmut was 5.5%, and 2.3% or 2.4% in patients with an apparently sporadic adenoma or macroadenoma, respectively. By contrast, three of four patients (75%) with a positive family history were tested positive for an AIPmut. Except for a positive family history, there were no significant differences between patients with and without an AIPmut.
  
  
  CONCLUSIONS
  The frequency of AIPmut in this registry-based cohort of young patients with acromegaly is lower than previously reported. Patients with a positive family history should be tested for an AIPmut, whereas young patients without an apparent family history should be screened, depending on the individual cost to benefit ratio.
authors.affiliation: Division of Endocrinology and Diabetes (C.S., B.M.), Department of Medicine I, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany; Department of Neurosurgery (J.H.), Eberhard Karls University Tuebingen, 72076 Tuebingen, Germany; Endocrine Practice (M.D.), 26122 Oldenburg, Germany; Center of Endocrinology and Diabetes (M.G.), 70178 Stuttgart, Germany; Endocrine Practice Kaisereiche (R.F.), 12159 Berlin, Germany; Interdisciplinary Center of Metabolism: Endocrinology, Diabetes, and Metabolism (U.P.), Charite-University-Medicine Berlin, 13352 Berlin, Germany; Department of Endocrinology (C.Be.), University Hospital of Essen, 45147 Essen, Germany; Division of Special Endocrinology (H.S.W.), Department of Endocrinology and Diabetes, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany; Fifth Medical Clinic (A.L.), University Medical Center Mannheim, University of Heidelberg, 68167 Heidelberg, Germany; Division of Endocrinology and Diabetes (D.K.), Department of Medicine I, Rheinische Friedrich-Wilhelms-University Bonn, 53127 Bonn, Germany; Department of Endocrinology (C.J.-H.), German Clinic of Diagnostics, Wiesbaden, 65191 Wiesbaden, Germany; Medical Department III (A.T.), University of Leipzig, 04103 Leipzig, Germany; Department of Gastroenterology, Hepatology, and Endocrinology (S.S.), Hannover Medical School, 30625 Hannover, Germany; Pituitary Surgery/Interdisciplinary Endocrinology (J.F.), UKE Hamburg, 20246 Hamburg, Germany; Endocrine Practice (C.Bu.), 20095 Hamburg, Germany; Max Planck Institute of Psychiatry (C.D., G.S.), 80804 Munich, Germany; Bioglobe GmbH (W.H.), 22529 Hamburg, Germany; and Medizinische Klinik IV (J.S.), Ludwig-Maximilians-University 80336 Munich, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Schöfl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Honegger
authors.forename: Michael
authors.initials: M
authors.lastname: Droste
authors.forename: Martin
authors.initials: M
authors.lastname: Grussendorf
authors.forename: Reinhard
authors.initials: R
authors.lastname: Finke
authors.forename: Ursula
authors.initials: U
authors.lastname: Plöckinger
authors.forename: Christian
authors.initials: C
authors.lastname: Berg
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: Alexander
authors.initials: A
authors.lastname: Lammert
authors.forename: Dietrich
authors.initials: D
authors.lastname: Klingmüller
authors.forename: Cornelia
authors.initials: C
authors.lastname: Jaursch-Hancke
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Sabine
authors.initials: S
authors.lastname: Schneidewind
authors.forename: Jörg
authors.initials: J
authors.lastname: Flitsch
authors.forename: Catharina
authors.initials: C
authors.lastname: Bullmann
authors.forename: Christina
authors.initials: C
authors.lastname: Dimopoulou
authors.forename: Günter
authors.initials: G
authors.lastname: Stalla
authors.forename: Bernhard
authors.initials: B
authors.lastname: Mayr
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoeppner
authors.forename: Jochen
authors.initials: J
authors.lastname: Schopohl
mesh_terms: D000172:Acromegaly / Q000453:epidemiology* / Q000235:genetics*; D000236:Adenoma / Q000453:epidemiology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005858:Germany / Q000453:epidemiology; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012042:Registries; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein