Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility

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dc.contributor.buuauthorTemel, Şehime
dc.contributor.departmentBursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.tr_TR
dc.contributor.orcid0000-0002-9802-0880tr_TR
dc.contributor.researcheridAAG-8385-2021tr_TR
dc.contributor.scopusid6507885442tr_TR
dc.date.accessioned2022-12-26T12:52:32Z
dc.date.available2022-12-26T12:52:32Z
dc.date.issued2020-06-15
dc.descriptionBu çalışmada 26 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır.tr_TR
dc.description.abstractMale infertility affects similar to 7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity.en_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.description.sponsorshipNIH Office of the Directoren_US
dc.description.sponsorshipEunice Kennedy Shriver National Institute of Child Health and Human Developmenten_US
dc.description.sponsorshipDeutsche Forschungsgemeinschaftde
dc.identifier.citationWyrwoll, M. J. vd. (2020). "Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility". American Journal of Human Genetics, 107(2), 342-351.en_US
dc.identifier.endpage351tr_TR
dc.identifier.issn0002-9297
dc.identifier.issn1537-6605
dc.identifier.issue2tr_TR
dc.identifier.pubmed32673564tr_TR
dc.identifier.scopus2-s2.0-85088861386tr_TR
dc.identifier.startpage341tr_TR
dc.identifier.urihttps://doi.org/10.1016/j.ajhg.2020.06.010
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0002929720301981
dc.identifier.urihttp://hdl.handle.net/11452/30096
dc.identifier.volume107tr_TR
dc.identifier.wos000558491800014tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherCell Pressen_US
dc.relation.bapKUAP(T)-2014/36tr_TR
dc.relation.collaborationYurt içitr_TR
dc.relation.collaborationYurt dışıtr_TR
dc.relation.collaborationSanayitr_TR
dc.relation.journalAmerican Journal of Human Geneticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectVariantsen_US
dc.subjectAzoospermiaen_US
dc.subjectGenetics & heredityen_US
dc.subject.emtreeMeiosis 1 arresting protein, mouseen_US
dc.subject.emtreeProteinen_US
dc.subject.emtreeAlleleen_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeAzoospermiaen_US
dc.subject.emtreeCell cycle arresttr_TR
dc.subject.emtreeCryptozoospermiaen_US
dc.subject.emtreeDisease severityen_US
dc.subject.emtreeFamilyen_US
dc.subject.emtreeFrameshift mutationen_US
dc.subject.emtreeGeneen_US
dc.subject.emtreeGene mutationen_US
dc.subject.emtreeGenetic associationen_US
dc.subject.emtreeGenetic codeen_US
dc.subject.emtreeGenetic variabilityen_US
dc.subject.emtreeGerm cellen_US
dc.subject.emtreeHomozygoteen_US
dc.subject.emtreeHumanen_US
dc.subject.emtreeIn vitro studyen_US
dc.subject.emtreeLoss of function mutationen_US
dc.subject.emtreeM1AP geneen_US
dc.subject.emtreeMale infertilityen_US
dc.subject.emtreeMeiosisen_US
dc.subject.emtreeMissense mutationen_US
dc.subject.emtreeNonhumanen_US
dc.subject.emtreeOligospermiaen_US
dc.subject.emtreePhenotypeen_US
dc.subject.emtreePriority journalen_US
dc.subject.emtreeSpermatiden_US
dc.subject.emtreeSpermatozoonen_US
dc.subject.emtreeTurkish citizenen_US
dc.subject.emtreeWhole exome sequencingen_US
dc.subject.emtreeAdulten_US
dc.subject.emtreeAlleleen_US
dc.subject.emtreeAnimalen_US
dc.subject.emtreeAzoospermiaen_US
dc.subject.emtreeCell cycle checkpointen_US
dc.subject.emtreeGeneticsen_US
dc.subject.emtreeMaleen_US
dc.subject.emtreeMale infertilityen_US
dc.subject.emtreeMeiosisen_US
dc.subject.emtreeMouseen_US
dc.subject.emtreeMutationen_US
dc.subject.emtreeProceduresen_US
dc.subject.emtreeSpermatogenesisen_US
dc.subject.emtreeTestisen_US
dc.subject.emtreeTurkey (bird)en_US
dc.subject.meshAdulten_US
dc.subject.meshAllelesen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAzoospermiaen_US
dc.subject.meshCell cycle checkpointsen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshInfertility, maleen_US
dc.subject.meshMaleen_US
dc.subject.meshMeiosisen_US
dc.subject.meshMiceen_US
dc.subject.meshMutationen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshProteinsen_US
dc.subject.meshSpermatogenesisen_US
dc.subject.meshSpermatozoaen_US
dc.subject.meshTestisen_US
dc.subject.meshTurkeyen_US
dc.subject.meshWhole exome sequencingen_US
dc.subject.scopusMale Infertility; Azoospermia; Y Chromosomeen_US
dc.subject.wosGenetics & heredityen_US
dc.titleBi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertilityen_US
dc.typeArticle
dc.wos.quartileQ1en_US

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