title: Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations.
abstract: OBJECTIVE
  To identify new molecular actors involved in nonsyndromic premature ovarian failure (POF) etiology.
  
  
  METHODS
  This is a retrospective case-control cohort study.
  
  
  METHODS
  University research group and IVF medical center.
  
  
  METHODS
  Twelve women affected by nonsyndromic POF. The control group included 176 women whose menopause had occurred after age 50 and had no antecedents regarding gynecological disease. A further 345 women from the same ethnic origin (general population group) were also recruited to assess allele frequency for potentially deleterious sequence variants.
  
  
  METHODS
  Next generation sequencing (NGS), Sanger sequencing, and bioinformatics analysis.
  
  
  METHODS
  The complete coding regions of 70 candidate genes were massively sequenced, via NGS, in POF patients. Bioinformatics and genetics were used to confirm NGS results and to identify potential sequence variants related to the disease pathogenesis.
  
  
  RESULTS
  We have identified mutations in two novel genes, ADAMTS19 and BMPR2, that are potentially related to POF origin. LHCGR mutations, which might have contributed to the phenotype, were also detected.
  
  
  CONCLUSIONS
  We thus recommend NGS as a powerful tool for identifying new molecular actors in POF and for future diagnostic/prognostic purposes.
authors.affiliation: Unidad de Genética, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia.
authors.forename: Dora Janeth
authors.initials: DJ
authors.lastname: Fonseca
authors.affiliation: Unidad de Genética, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia.
authors.forename: Liliana Catherine
authors.initials: LC
authors.lastname: Patiño
authors.affiliation: Unidad de Genética, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia.
authors.forename: Yohjana Carolina
authors.initials: YC
authors.lastname: Suárez
authors.affiliation: Unidad de Genética, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia.
authors.forename: Asid
authors.initials: A
authors.lastname: de Jesús Rodríguez
authors.affiliation: Unidad de Genética, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia.
authors.forename: Heidi Eliana
authors.initials: HE
authors.lastname: Mateus
authors.affiliation: Unidad de Genética, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia.
authors.forename: Karen Marcela
authors.initials: KM
authors.lastname: Jiménez
authors.affiliation: Unidad de Genética, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia.
authors.forename: Oscar
authors.initials: O
authors.lastname: Ortega-Recalde
authors.affiliation: Unidad de Fertilidad PMA, Clínica Marly, Bogota, Colombia.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Díaz-Yamal
authors.affiliation: Unidad de Genética, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia. Electronic address: paul.laissue@urosario.edu.co.
authors.forename: Paul
authors.initials: P
authors.lastname: Laissue
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071096:ADAMTS Proteins; D000328:Adult; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016649:Primary Ovarian Insufficiency / Q000175:diagnosis* / Q000235:genetics*; D012189:Retrospective Studies; D017421:Sequence Analysis / Q000379:methods
chemical_list: C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C544648:ADAMTS19 protein, human
keywords: ADAMTS19; BMPR2; POF; Premature ovarian failure; next generation sequencing