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New mutations in non-syndromic primary ovarian insufficiency patients identified via whole-exome sequencing

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dc.creatorPatiño, Liliana Catherinespa
dc.creatorBeau, Isabellespa
dc.creatorCarlosama, Carolinaspa
dc.creatorBuitrago, July Constanzaspa
dc.creatorGonzález, Ronaldspa
dc.creatorSuarez Martinez, Carlos Fernando
dc.creatorPatarroyo, Manuel A.
dc.creatorDelemer, Brigittespa
dc.creatorYoung, Jacquesspa
dc.creatorBinart, Nadinespa
dc.creatorLaissue, Paul
dc.date.accessioned2020-05-26T00:10:29Z
dc.date.available2020-05-26T00:10:29Z
dc.date.created2017spa
dc.description.abstractSTUDY QUESTION Is it possible to identify new mutations potentially associated with non-syndromic primary ovarian insufficiency (POI) via whole-exome sequencing (WES)? SUMMARY ANSWER WES is an efficient tool to study genetic causes of POI as we have identified new mutations, some of which lead to protein destablization potentially contributing to the disease etiology. WHAT IS KNOWN ALREADY POI is a frequently occurring complex pathology leading to infertility. Mutations in only few candidate genes, mainly identified by Sanger sequencing, have been definitively related to the pathogenesis of the disease. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study performed on 69 women affected by POI. PARTICIPANTS/MATERIALS, SETTING, METHODS WES and an innovative bioinformatics analysis were used on non-synonymous sequence variants in a subset of 420 selected POI candidate genes. Mutations in BMPR1B and GREM1 were modeled by using fragment molecular orbital analysis. MAIN RESULTS AND THE ROLE OF CHANCE Fifty-five coding variants in 49 genes potentially related to POI were identified in 33 out of 69 patients (48%). These genes participate in key biological processes in the ovary, such as meiosis, follicular development, granulosa cell differentiation/proliferation and ovulation. The presence of at least two mutations in distinct genes in 42% of the patients argued in favor of a polygenic nature of POI. LIMITATIONS, REASONS FOR CAUTION It is possible that regulatory regions, not analyzed in the present study, carry further variants related to POI. WIDER IMPLICATIONS OF THE FINDINGS WES and the in silico analyses presented here represent an efficient approach for mapping variants associated with POI etiology. Sequence variants presented here represents potential future genetic biomarkers. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Universidad del Rosario and Colciencias (Grants CS/CIGGUR-ABN062-2016 and 672-2014). Colciencias supported Liliana Catherine Patiñós work (Fellowship: 617, 2013). The authors declare no conflict of interest. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/humrep/dex089
dc.identifier.issn14602350
dc.identifier.issn02681161
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24231
dc.language.isoengspa
dc.publisherOxford University Pressspa
dc.relation.citationEndPage1520
dc.relation.citationIssueNo. 7
dc.relation.citationStartPage1512
dc.relation.citationTitleHuman Reproduction
dc.relation.citationVolumeVol. 32
dc.relation.ispartofHuman Reproduction, ISSN:14602350, 02681161, Vol.32, No.7 (2017); pp. 1512-1520spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85021823054&doi=10.1093%2fhumrep%2fdex089&partnerID=40&md5=fbf260cec8160fe64adef8d177270e56spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordEstradiolspa
dc.subject.keywordtype ieng
dc.subject.keywordLuteinizing hormonespa
dc.subject.keywordBmpr1b proteineng
dc.subject.keywordBone morphogenetic protein receptor 1spa
dc.subject.keywordGrem1 proteineng
dc.subject.keywordSignal peptidespa
dc.subject.keywordAdolescentspa
dc.subject.keywordAdultspa
dc.subject.keywordArticlespa
dc.subject.keywordBioinformaticsspa
dc.subject.keywordBmpr1b genespa
dc.subject.keywordCell differentiationspa
dc.subject.keywordCell proliferationspa
dc.subject.keywordCohort analysisspa
dc.subject.keywordFemalespa
dc.subject.keywordFrameshift mutationspa
dc.subject.keywordGenespa
dc.subject.keywordGene frequencyspa
dc.subject.keywordGene locusspa
dc.subject.keywordGene mappingspa
dc.subject.keywordGene mutationspa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordGranulosa cellspa
dc.subject.keywordGrem1 genespa
dc.subject.keywordHumanspa
dc.subject.keywordMajor clinical studyspa
dc.subject.keywordMeiosisspa
dc.subject.keywordMissense mutationspa
dc.subject.keywordNonsense mutationspa
dc.subject.keywordOvary follicle developmentspa
dc.subject.keywordOvary insufficiencyspa
dc.subject.keywordOvulationspa
dc.subject.keywordRetrospective studyspa
dc.subject.keywordWhole exome sequencingspa
dc.subject.keywordYoung adultspa
dc.subject.keywordAmino acid substitutionspa
dc.subject.keywordBiologyspa
dc.subject.keywordChemistryspa
dc.subject.keywordClinical trialspa
dc.subject.keywordExpert systemspa
dc.subject.keywordFrancespa
dc.subject.keywordGenetic predispositionspa
dc.subject.keywordGeneticsspa
dc.subject.keywordGenome-wide association studyspa
dc.subject.keywordMetabolismspa
dc.subject.keywordMolecular dynamicsspa
dc.subject.keywordMolecular modelspa
dc.subject.keywordMulticenter studyspa
dc.subject.keywordMutationspa
dc.subject.keywordPatient referralspa
dc.subject.keywordPremature ovarian failurespa
dc.subject.keywordProtein stabilityspa
dc.subject.keywordSingle nucleotide polymorphismspa
dc.subject.keywordWhole exome sequencingspa
dc.subject.keywordAdultspa
dc.subject.keywordAmino acid substitutionspa
dc.subject.keywordBone morphogenetic protein receptorseng
dc.subject.keywordCohort studiesspa
dc.subject.keywordComputational biologyspa
dc.subject.keywordExpert systemsspa
dc.subject.keywordFemalespa
dc.subject.keywordFrancespa
dc.subject.keywordGenetic predisposition to diseasespa
dc.subject.keywordGenome-wide association studyspa
dc.subject.keywordHumansspa
dc.subject.keywordIntercellular signaling peptides and proteinsspa
dc.subject.keywordModelseng
dc.subject.keywordMolecular dynamics simulationspa
dc.subject.keywordMutationspa
dc.subject.keywordPolymorphismeng
dc.subject.keywordPrimary ovarian insufficiencyspa
dc.subject.keywordProtein stabilityspa
dc.subject.keywordReferral and consultationspa
dc.subject.keywordRetrospective studiesspa
dc.subject.keywordWhole exome sequencingspa
dc.subject.keywordYoung adultspa
dc.subject.keywordFemale infertilityspa
dc.subject.keywordMolecular etiologyspa
dc.subject.keywordPolygenic diseasespa
dc.subject.keywordPrimary ovarian insufficiencyspa
dc.subject.keywordWhole-exome sequencingspa
dc.titleNew mutations in non-syndromic primary ovarian insufficiency patients identified via whole-exome sequencingspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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