title: Germline Prolactin Receptor Mutation Is Not a Major Cause of Sporadic Prolactinoma in Humans.
abstract: No genetic anomalies specifically predisposing humans to prolactinomas have so far been identified. The prolactin receptor (PRLR) is a good candidate, however, as Prlr knockout mice develop prolactinomas, and a case of familial hyperprolactinemia has been linked to PRLR mutation. The main objective of this study was to detect germline PRLR mutations in patients with sporadic prolactinomas unrelated to AIP or MEN1 mutation.
  
  
  
  We sequenced all PRLR exons and intron-exon junctions on genomic DNA from 88 patients with a median age of 24 years.
  
  
  
  We identified 4 PRLR variations (p.Ile76Val, p.Ile146Leu, p.Glu108Lys and p.Glu554Gln) in 16 patients. One patient had the rare variant p.Glu554Gln in the heterozygous state. Another patient had the extremely rare p.Glu108Lys variant described here for the first time. The other 2 variants (p.Ile76Val and p.Ile146Leu) are relatively common in the general population. All these 4 variants have been functionally tested in vitro and have no effect on PRLR expression, localization and signaling after prolactin stimulation.
  
  
  
  Inactivating germline variations of PRLR are not associated with sporadic prolactinoma in this series. Nevertheless, somatic disruption of PRLR has not been excluded in this subset of pituitary tumors.
authors.affiliation: Inserm UMR-1185, Faculté de Médecine Paris Sud, Université Paris-Saclay, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bernard
authors.forename: Justine
authors.initials: J
authors.lastname: Bouilly
authors.forename: Isabelle
authors.initials: I
authors.lastname: Beau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Broutin
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D019556:COS Cells; D002648:Child; D002522:Chlorocebus aethiops; D015331:Cohort Studies; D003198:Computer Simulation; D018095:Germ-Line Mutation / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D008875:Middle Aged; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed / Q000379:methods; D010911:Pituitary Neoplasms / Q000235:genetics*; D015175:Prolactinoma / Q000235:genetics*; D011981:Receptors, Prolactin / Q000235:genetics* / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014162:Transfection; D055815:Young Adult
chemical_list: D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor