title: A homozygous mutation ofGNRHRin a familial case diagnosed with polycystic ovary syndrome.
abstract: BACKGROUND
  PCOS is a heterogeneous condition characterized by hyperandrogenism and chronic anovulation and affects about 10% of women. Its etiology is poorly known, but a dysregulation of gonadotropin secretion is one of its hallmarks.
  
  
  OBJECTIVE
  As the etiology of PCOS is unclear, we have performed a genome-wide analysis of a consanguineous family with three sisters diagnosed with PCOS.
  
  
  METHODS
  Whole-exome sequencing and Sanger sequencing confirmation.
  
  
  RESULTS
  Whole-exome sequencing allowed the detection of the missense variant rs104893836 located in the first coding exon of theGNRHRgene and leading to the p.Gln106Arg (p.Q106R) substitution. Sanger sequencing of all available individuals of the family confirmed that the variant was homozygous in the three affected sisters and heterozygous in both parents.
  
  
  CONCLUSIONS
  This is the first description of aGNRHRgene mutation in patients diagnosed with PCOS. Although we do not exclude a possible interaction of the identified variant with the genetic background and/or the environment, our result suggests that genetic alterations in the hypothalamo-pituitary axis may play role in the pathogenesis of PCOS.
authors.affiliation: Institut Jacques MonodUniversité Paris Diderot, Paris, France.|Université Paris Diderot-Paris VIIParis Cedex, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Caburet
authors.affiliation: OBGYN DepartmentHaEmek Medical Center, Afula, Israel.
authors.forename: Ronit Beck
authors.initials: RB
authors.lastname: Fruchter
authors.affiliation: Institut Jacques MonodUniversité Paris Diderot, Paris, France.|Université Paris Diderot-Paris VIIParis Cedex, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Legois
authors.affiliation: Institut CochinParis, France.|Université Paris Descartes-Paris VParis, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Fellous
authors.affiliation: The Rappaport Faculty of MedicineTechnion, Haifa, Israel.|Genetic InstituteHaemek Medical Center, Afula, Israel.
authors.forename: Stavit
authors.initials: S
authors.lastname: Shalev
authors.affiliation: Institut Jacques MonodUniversité Paris Diderot, Paris, France.|Université Paris Diderot-Paris VIIParis Cedex, France.
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
mesh_terms: D003241:Consanguinity; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006720:Homozygote; D006801:Humans; D007557:Israel; D007986:Luteinizing Hormone / Q000097:blood; D009154:Mutation; D010375:Pedigree; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D011966:Receptors, LHRH / Q000235:genetics*; D012529:Saudi Arabia / Q000208:ethnology; D017422:Sequence Analysis, DNA
chemical_list: C484844:GNRHR protein, human; D011966:Receptors, LHRH; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone