title: Triallelic digenic mutation in the prokineticin 2 and GNRH receptor genes in two brothers with normosmic congenital hypogonadotropic hypogonadism.
abstract: Purpose/aim of the study: To date, different genes have been identified as responsible for the presence of normosmic congenital hypogonadotropic hypogonadism (nCHH). Herein, we report the molecular findings regarding the analysis of PROK2, in two brothers with nCHH.
  
  
  METHODS
  Two siblings with nCHH, in whom mutations in GNRHR, PROKR2 and FGFR1 had been investigated previously, as well as their family were studied. DNA was amplified by PCR and sequenced for the PROK2 gene. Controls were analyzed by restriction fragment-length polymorphism. The structure of PROK2 and its mutant protein were compared using a protein molecular model.
  
  
  RESULTS
  Both affected siblings exhibited a heterozygous p.R117W mutation in PROK2, while their mother was a heterozygous carrier and their father, an unaffected brother and their sister were homozygous wild type. Besides, both patients presented a homozygous p.E90K mutation in GNRHR that had been previously reported.
  
  
  CONCLUSIONS
  We found a novel mutation in PROK2 in two siblings in whom a mutation in the GNRHR gene had been previously reported.
authors.affiliation: Unidad de Investigación en Obesidad: Facultad de Medicina, Universidad Nacional Autónoma de México; Clínica de Obesidad, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," México, D.F. , México .
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Méndez
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zenteno
authors.forename: Agustín
authors.initials: A
authors.lastname: Coronel
authors.forename: Marvin Antonio
authors.initials: MA
authors.lastname: Soriano-Ursúa
authors.forename: Elith Yazmín
authors.initials: EY
authors.lastname: Valencia-Villalvazo
authors.forename: Daniela
authors.initials: D
authors.lastname: Soderlund
authors.forename: Ramón Mauricio
authors.initials: RM
authors.lastname: Coral-Vázquez
authors.forename: Patricia
authors.initials: P
authors.lastname: Canto
mesh_terms: D005768:Gastrointestinal Hormones / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D009479:Neuropeptides / Q000235:genetics*; D011966:Receptors, LHRH / Q000235:genetics*; D035781:Siblings; D055815:Young Adult
chemical_list: D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human; D011966:Receptors, LHRH
keywords: GNRHR; PROK2; molecular modeling; nCHH; triallelic digenic mutations