title: Mutations in gonadotropin-releasing hormone signaling pathway in two nIHH patients with successful pregnancy outcomes.
abstract: BACKGROUND
  Anomalous levels of gonadotropin-releasing hormone (GnRH) secretion result in a variety of reproductive phenotypes associated with infertility or subfertility. The normosmic isolated hypogonadotropic hypogonadism (nIHH) is due to a failure of either GnRH pulsatile secretion in hypothalamus or its reception in pituitary. The spectrum of nIHH-associated alterations continues to expand, especially when additional ethnic populations are investigated. The aim of this study was to uncover genetic causes for nIHH in patients of Russian origin.
  
  
  METHODS
  For two nIHH patients referred to infertility clinic, both exons and promoter sequences of 6 GnRH signaling genes were sequenced.
  
  
  RESULTS
  Patient 1 was a compound heterozygote for mutations in GnRH and its receptor encoding genes, while in Patient 2 GnRHR mutations were found in homozygous state. In both patients, the coding frame of GnRHR gene harbored missense-mutation Arg139His previously described as founder mutation in Polish and Brazilan patients. IVF/ET treatments were successful, with phenotypically healthy offsprings delivered.
  
  
  CONCLUSIONS
  Polish founder mutation Arg139His in GnRHR was found in two nIHH patients originating from Western region of Russia. Common variant of GnRH-encoding gene, Trp16Ser, could possibly contribute to reproductive phenotypes in patients with heterozygous mutations of other GnRH signaling pathway genes.
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics", Moskvorechie 1, Moscow, Russia.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Zernov
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics", Moskvorechie 1, Moscow, Russia.|The Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Moscow Region, Russia.|The Russian National Research Medical University named after N.I.Pirogov (RNRMU), Ostrovityanova 1, Moscow, 117997, Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Skoblov
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics", Moskvorechie 1, Moscow, Russia. aancha@gmail.com.|The Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Moscow Region, Russia. aancha@gmail.com.|Center for the Study of Chronic Metabolic and Rare Diseases, School of Systems Biology, College of Science, George Mason University, 4400 University Dr David King Hall MSN3 E1, Fairfax, VA, USA. aancha@gmail.com.|Atlas Biomed Group, 31 Malaya Nikitskaya Str, Bldg. 1, Moscow, 123317, Russia. aancha@gmail.com.
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
authors.affiliation: Center of Human Reproduction "Genesis", St. Petersburg, Russia.|Department of Obstetrics and Gynecology, State Pediatric Medical University, St. Petersburg, Russia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Boyarsky
mesh_terms: D000328:Adult; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D007231:Infant, Newborn; D007247:Infertility, Female / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods
chemical_list: D007987:Gonadotropin-Releasing Hormone