title: Large genomic deletions in AIP in pituitary adenoma predisposition.
abstract: BACKGROUND
  Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings.
  
  
  OBJECTIVE
  Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP.
  
  
  METHODS
  Here, we applied the multiplex ligation-dependent probe amplification assay to examine whether large genomic AIP or MEN1 alterations account for a subset of PAP cases.
  
  
  METHODS
  The study was performed on familial and sporadic pituitary adenoma cases of European origin, which had previously tested negative for germline AIP and MEN1 mutations by sequencing.
  
  
  RESULTS
  Two of 21 pituitary adenoma families (9.5%) were found to harbor an AIP deletion. No copy number changes were detected among 67 sporadic pituitary adenoma patients. No MEN1 deletions were found.
  
  
  CONCLUSIONS
  The present study shows that large genomic AIP deletions account for a subset of PAP. Therefore, in suspected PAP cases undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe amplification could be considered if direct sequencing does not identify a mutation.
authors.affiliation: Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Georgitsi
authors.forename: Elina
authors.initials: E
authors.lastname: Heliövaara
authors.forename: Ralf
authors.initials: R
authors.lastname: Paschke
authors.forename: Ajith V K
authors.initials: AV
authors.lastname: Kumar
authors.forename: Marc
authors.initials: M
authors.lastname: Tischkowitz
authors.forename: Outi
authors.initials: O
authors.lastname: Vierimaa
authors.forename: Pasi
authors.initials: P
authors.lastname: Salmela
authors.forename: Timo
authors.initials: T
authors.lastname: Sane
authors.forename: Ernesto
authors.initials: E
authors.lastname: De Menis
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cannavò
authors.forename: Sadi
authors.initials: S
authors.lastname: Gündogdu
authors.forename: Anneke
authors.initials: A
authors.lastname: Lucassen
authors.forename: Louise
authors.initials: L
authors.lastname: Izatt
authors.forename: Simon
authors.initials: S
authors.lastname: Aylwin
authors.forename: Gul
authors.initials: G
authors.lastname: Bano
authors.forename: Shirley
authors.initials: S
authors.lastname: Hodgson
authors.forename: Christian A
authors.initials: CA
authors.lastname: Koch
authors.forename: Auli
authors.initials: A
authors.lastname: Karhu
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein