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ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure

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dc.creatorDelcour C.spa
dc.creatorAmazit L.spa
dc.creatorPatino L.C.spa
dc.creatorMagnin F.spa
dc.creatorFagart J.spa
dc.creatorDelemer B.spa
dc.creatorYoung J.spa
dc.creatorLaissue P.spa
dc.creatorBinart N.spa
dc.creatorBeau I.spa
dc.date.accessioned2020-05-26T00:09:16Z
dc.date.available2020-05-26T00:09:16Z
dc.date.created2019spa
dc.description.abstractPurpose: Primary ovarian insufficiency (POI) is a frequent disorder that affects ~1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone (FSH), leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene variants, most cases remain idiopathic. The aim of the present study was to identify and validate functionally new sequence variants in ATG (autophagy-related genes) leading to POI. Methods: We have reanalyzed, in silico, the exome sequencing data from a previously reported work performed in 69 unrelated POI women. Functional experiments using a classical hallmark of autophagy, the microtubule-associated protein 1 light chain 3? (LC3), were then used to link these genes to this lysosomal degradation pathway. Results: We venture a functional link between ATG7 and ATG9A variants and POI. We demonstrated that variant ATG7 and ATG9A led to a decrease in autophagosome biosynthesis and consequently to an impairment of autophagy, a key biological process implicated in the preservation of the primordial follicles forming the ovarian reserve. Conclusion: Our results unveil that impaired autophagy is a novel pathophysiological mechanism involved in human POI. © 2018, American College of Medical Genetics and Genomics.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1038/s41436-018-0287-y
dc.identifier.issn10983600
dc.identifier.issn15300366
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24148
dc.language.isoengspa
dc.publisherNature Publishing Groupspa
dc.relation.citationEndPage938
dc.relation.citationIssueNo. 4
dc.relation.citationStartPage930
dc.relation.citationTitleGenetics in Medicine
dc.relation.citationVolumeVol. 21
dc.relation.ispartofGenetics in Medicine, ISSN:10983600, 15300366, Vol.21, No.4 (2019); pp. 930-938spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85053452773&doi=10.1038%2fs41436-018-0287-y&partnerID=40&md5=3b614a91984db3a514a884ed9d6d9edbspa
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.keywordAutophagy related protein 7spa
dc.subject.keywordprematureeng
dc.subject.keywordAtg9a protein, humanspa
dc.subject.keywordAutophagy related proteinspa
dc.subject.keywordAutophagy related protein 7spa
dc.subject.keywordFollitropinspa
dc.subject.keywordMembrane proteinspa
dc.subject.keywordVesicular transport proteinspa
dc.subject.keywordArticlespa
dc.subject.keywordAtg7 genespa
dc.subject.keywordAtg9a genespa
dc.subject.keywordAutophagosomespa
dc.subject.keywordAutophagyspa
dc.subject.keywordComputer modelspa
dc.subject.keywordControlled studyspa
dc.subject.keywordFemalespa
dc.subject.keywordGenespa
dc.subject.keywordGene identificationspa
dc.subject.keywordGene locationspa
dc.subject.keywordGene sequencespa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordHaploinsufficiencyspa
dc.subject.keywordHumanspa
dc.subject.keywordHuman cellspa
dc.subject.keywordLoss of function mutationspa
dc.subject.keywordMajor clinical studyspa
dc.subject.keywordMutational analysisspa
dc.subject.keywordOvarian reservespa
dc.subject.keywordOvary insufficiencyspa
dc.subject.keywordPathogenesisspa
dc.subject.keywordWhole exome sequencingspa
dc.subject.keywordAdultspa
dc.subject.keywordAutophagyspa
dc.subject.keywordEarly menopausespa
dc.subject.keywordGenetic predispositionspa
dc.subject.keywordGeneticsspa
dc.subject.keywordLoss of function mutationspa
dc.subject.keywordPathologyspa
dc.subject.keywordPremature ovarian failurespa
dc.subject.keywordAdultspa
dc.subject.keywordAutophagyspa
dc.subject.keywordAutophagy-related protein 7spa
dc.subject.keywordAutophagy-related proteinsspa
dc.subject.keywordFemalespa
dc.subject.keywordFollicle stimulating hormonespa
dc.subject.keywordGenetic predisposition to diseasespa
dc.subject.keywordHumansspa
dc.subject.keywordLoss of function mutationspa
dc.subject.keywordMembrane proteinsspa
dc.subject.keywordMenopauseeng
dc.subject.keywordPrimary ovarian insufficiencyspa
dc.subject.keywordVesicular transport proteinsspa
dc.subject.keywordWhole exome sequencingspa
dc.subject.keywordAutophagyspa
dc.subject.keywordInfertilityspa
dc.subject.keywordOvarian reservespa
dc.titleATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failurespa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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