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A homozygous donor splice-site mutation in the meiotic gene MSH4 causes primary ovarian insufficiency

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dc.creatorCarlosama, Carolinaspa
dc.creatorElzaiat, Maëvaspa
dc.creatorPatiño, Liliana Cspa
dc.creatorMateus, Heidi Espa
dc.creatorVeitia, Reiner Aspa
dc.creatorLaissue, Paul
dc.date.accessioned2020-05-26T00:10:21Z
dc.date.available2020-05-26T00:10:21Z
dc.date.created2017spa
dc.description.abstractPremature ovarian insufficiency (POI) is a frequent pathology that affects women under 40 years of age, characterized by an early cessation of menses and high FSH levels. Despite recent progresses in molecular diagnosis, the etiology of POI remains idiopathic in most cases. Whole-exome sequencing of members of a Colombian family affected by POI allowed us to identify a novel homozygous donor splice-site mutation in the meiotic gene MSH4 (MutS Homolog 4). The variant followed a strict mendelian segregation within the family and was absent in a cohort of 135 women over 50 years of age without history of infertility, from the same geographical region as the affected family. Exon trapping experiments showed that the splice-site mutation induced skipping of exon 17. At the protein level, the mutation p.Ile743_Lys785del is predicted to lead to the ablation of the highly conserved Walker B motif of the ATP-binding domain, thus inactivating MSH4. Our study describes the first MSH4 mutation associated with POI and increases the number of meiotic/DNA repair genes formally implicated as being responsible for this condition. © The Author 2017. Published by Oxford University Press. All rights reserved.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/hmg/ddx199
dc.identifier.issn14602083
dc.identifier.issn09646906
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24224
dc.language.isoengspa
dc.publisherOxford University Pressspa
dc.relation.citationEndPage3166
dc.relation.citationIssueNo. 16
dc.relation.citationStartPage3161
dc.relation.citationTitleHuman Molecular Genetics
dc.relation.citationVolumeVol. 26
dc.relation.ispartofHuman Molecular Genetics, ISSN:14602083, 09646906, Vol.26, No.16 (2017); pp. 3161-3166spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85027713623&doi=10.1093%2fhmg%2fddx199&partnerID=40&md5=6c71eb24ec369343a57a967a4be6fb52spa
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.keywordComplementary DNAspa
dc.subject.keywordhumaneng
dc.subject.keywordFollitropinspa
dc.subject.keywordLuteinizing hormonespa
dc.subject.keywordMessenger RNAspa
dc.subject.keywordMSH4 proteinspa
dc.subject.keywordProteinspa
dc.subject.keywordThyrotropinspa
dc.subject.keywordUnclassified drugspa
dc.subject.keywordCell cycle proteinspa
dc.subject.keywordMSH4 proteineng
dc.subject.keywordAdultspa
dc.subject.keywordArticlespa
dc.subject.keywordCase reportspa
dc.subject.keywordCohort analysisspa
dc.subject.keywordControlled studyspa
dc.subject.keywordExon skippingspa
dc.subject.keywordFemalespa
dc.subject.keywordFollitropin blood levelspa
dc.subject.keywordGenespa
dc.subject.keywordGene frequencyspa
dc.subject.keywordGene mutationspa
dc.subject.keywordGene sequencespa
dc.subject.keywordGenetic variationspa
dc.subject.keywordHela cell linespa
dc.subject.keywordHeterozygosityspa
dc.subject.keywordHeterozygotespa
dc.subject.keywordHumanspa
dc.subject.keywordHuman cellspa
dc.subject.keywordInheritancespa
dc.subject.keywordKaryotype 46eng
dc.subject.keywordLuteinizing hormone blood levelspa
dc.subject.keywordMenarchespa
dc.subject.keywordMenstrual irregularityspa
dc.subject.keywordMSH4 genespa
dc.subject.keywordPedigreespa
dc.subject.keywordPremature ovarian failurespa
dc.subject.keywordPriority journalspa
dc.subject.keywordReverse transcription polymerase chain reactionspa
dc.subject.keywordSanger sequencingspa
dc.subject.keywordSecondary amenorrheaspa
dc.subject.keywordSegregation analysisspa
dc.subject.keywordThyrotropin blood levelspa
dc.subject.keywordTransvaginal echographyspa
dc.subject.keywordUterus myomaspa
dc.subject.keywordChemistryspa
dc.subject.keywordEarly menopausespa
dc.subject.keywordExonspa
dc.subject.keywordGeneticsspa
dc.subject.keywordHomozygotespa
dc.subject.keywordMetabolismspa
dc.subject.keywordMutationspa
dc.subject.keywordPremature ovarian failurespa
dc.subject.keywordRNA splice sitespa
dc.subject.keywordWhole exome sequencingspa
dc.subject.keywordAdultspa
dc.subject.keywordCell Cycle Proteinsspa
dc.subject.keywordCohort Studiesspa
dc.subject.keywordExonsspa
dc.subject.keywordFemalespa
dc.subject.keywordHomozygotespa
dc.subject.keywordHumansspa
dc.subject.keywordMenopauseeng
dc.subject.keywordMutationspa
dc.subject.keywordPedigreespa
dc.subject.keywordPrimary Ovarian Insufficiencyspa
dc.subject.keywordRNA Splice Sitesspa
dc.subject.keywordWhole Exome Sequencingspa
dc.titleA homozygous donor splice-site mutation in the meiotic gene MSH4 causes primary ovarian insufficiencyspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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