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Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly

DC FieldValueLanguage
dc.contributor.author지헌영-
dc.date.accessioned2018-07-20T08:19:18Z-
dc.date.available2018-07-20T08:19:18Z-
dc.date.issued2017-
dc.identifier.issn1061-4036-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/161090-
dc.description.abstractGalloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Pub. Co.-
dc.relation.isPartOfNATURE GENETICS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis/genetics-
dc.subject.MESHCRISPR-Cas Systems-
dc.subject.MESHCarrier Proteins/genetics-
dc.subject.MESHCell Movement-
dc.subject.MESHCytoskeleton/ultrastructure-
dc.subject.MESHDNA Repair/genetics-
dc.subject.MESHEndoplasmic Reticulum Stress/genetics-
dc.subject.MESHGene Knockout Techniques-
dc.subject.MESHHernia, Hiatal/genetics-
dc.subject.MESHHumans-
dc.subject.MESHIntracellular Signaling Peptides and Proteins/deficiency-
dc.subject.MESHIntracellular Signaling Peptides and Proteins/genetics-
dc.subject.MESHMetalloendopeptidases/deficiency-
dc.subject.MESHMetalloendopeptidases/genetics-
dc.subject.MESHMice-
dc.subject.MESHMicrocephaly/genetics-
dc.subject.MESHModels, Molecular-
dc.subject.MESHMultiprotein Complexes/genetics-
dc.subject.MESHMutation-
dc.subject.MESHNephrosis/genetics-
dc.subject.MESHNephrotic Syndrome/genetics-
dc.subject.MESHNephrotic Syndrome/pathology-
dc.subject.MESHPodocytes/metabolism-
dc.subject.MESHPodocytes/ultrastructure-
dc.subject.MESHProtein Conformation-
dc.subject.MESHProtein-Serine-Threonine Kinases/deficiency-
dc.subject.MESHProtein-Serine-Threonine Kinases/genetics-
dc.subject.MESHRNA Processing, Post-Transcriptional/genetics-
dc.subject.MESHRNA, Transfer/metabolism-
dc.subject.MESHTelomere Homeostasis/genetics-
dc.subject.MESHZebrafish-
dc.subject.MESHZebrafish Proteins/deficiency-
dc.subject.MESHZebrafish Proteins/genetics-
dc.titleMutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Pharmacology-
dc.contributor.googleauthorBraun-
dc.contributor.googleauthorRao-
dc.contributor.googleauthorMollet-
dc.contributor.googleauthorSchapiro-
dc.contributor.googleauthorDaugeron-
dc.contributor.googleauthorTan-
dc.contributor.googleauthorGribouval-
dc.contributor.googleauthorBoyer-
dc.contributor.googleauthorRevy-
dc.contributor.googleauthorJobst-Schwan-
dc.contributor.googleauthorSchmidt-
dc.contributor.googleauthorLawson-
dc.contributor.googleauthorSchanze-
dc.contributor.googleauthorAshraf-
dc.contributor.googleauthorUllmann-
dc.contributor.googleauthorHoogstraten-
dc.contributor.googleauthorBoddaert-
dc.contributor.googleauthorCollinet-
dc.contributor.googleauthorMartin-
dc.contributor.googleauthorLiger-
dc.contributor.googleauthorLovric-
dc.contributor.googleauthorFurlano-
dc.contributor.googleauthorGuerrera-
dc.contributor.googleauthorSanchez-Ferras-
dc.contributor.googleauthorHu-
dc.contributor.googleauthorBoschat-
dc.contributor.googleauthorSanquer-
dc.contributor.googleauthorMenten-
dc.contributor.googleauthorVergult-
dc.contributor.googleauthorDe Rocker-
dc.contributor.googleauthorAirik-
dc.contributor.googleauthorHermle-
dc.contributor.googleauthorShril-
dc.contributor.googleauthorWidmeier-
dc.contributor.googleauthorGee HY-
dc.contributor.googleauthorChoi-
dc.contributor.googleauthorSadowski-
dc.contributor.googleauthorPabst-
dc.contributor.googleauthorWarejko-
dc.contributor.googleauthorDaga-
dc.contributor.googleauthorBasta-
dc.contributor.googleauthorMatejas-
dc.contributor.googleauthorScharmann-
dc.contributor.googleauthorKienast-
dc.contributor.googleauthorBehnam-
dc.contributor.googleauthorBeeson-
dc.contributor.googleauthorBegtrup-
dc.contributor.googleauthorBruce-
dc.contributor.googleauthorCh'ng-
dc.contributor.googleauthorLin-
dc.contributor.googleauthorChang-
dc.contributor.googleauthorChen-
dc.contributor.googleauthorCho-
dc.contributor.googleauthorGaffney-
dc.contributor.googleauthorGipson-
dc.contributor.googleauthorHsu-
dc.contributor.googleauthorKari-
dc.contributor.googleauthorKe-
dc.contributor.googleauthorKiraly-Borri-
dc.contributor.googleauthorLai-
dc.contributor.googleauthorLemyre-
dc.contributor.googleauthorLittlejohn-
dc.contributor.googleauthorMasri-
dc.contributor.googleauthorMoghtaderi-
dc.contributor.googleauthorNakamura-
dc.contributor.googleauthorOzaltin-
dc.contributor.googleauthorPraet-
dc.contributor.googleauthorPrasad-
dc.contributor.googleauthorPrytula-
dc.contributor.googleauthorRoeder-
dc.contributor.googleauthorRump-
dc.contributor.googleauthorSchnur-
dc.contributor.googleauthorShiihara-
dc.contributor.googleauthorSinha-
dc.contributor.googleauthorSoliman-
dc.contributor.googleauthorSoulami-
dc.contributor.googleauthorSweetser-
dc.contributor.googleauthorTsai-
dc.contributor.googleauthorTsai-
dc.contributor.googleauthorTopaloglu-
dc.contributor.googleauthorVester-
dc.contributor.googleauthorViskochil-
dc.contributor.googleauthorVatanavicharn-
dc.contributor.googleauthorWaxler-
dc.contributor.googleauthorWierenga-
dc.contributor.googleauthorWolf-
dc.contributor.googleauthorWong-
dc.contributor.googleauthorLeidel-
dc.contributor.googleauthorTruglio-
dc.contributor.googleauthorDedon-
dc.contributor.googleauthorPoduri-
dc.contributor.googleauthorMane-
dc.contributor.googleauthorLifton-
dc.contributor.googleauthorBouchard-
dc.contributor.googleauthorKannu-
dc.contributor.googleauthorChitayat-
dc.contributor.googleauthorMagen-
dc.contributor.googleauthorCallewaert-
dc.contributor.googleauthorvan Tilbeurgh-
dc.contributor.googleauthorZenker-
dc.contributor.googleauthorAntignac-
dc.contributor.googleauthorHildebrandt-
dc.identifier.doi10.1038/ng.3933-
dc.contributor.localIdA03971-
dc.relation.journalcodeJ02294-
dc.identifier.eissn1546-1718-
dc.identifier.pmid28805828-
dc.contributor.alternativeNameGee, Heon Yung-
dc.contributor.affiliatedAuthorGee, Heon Yung-
dc.citation.volume49-
dc.citation.number10-
dc.citation.startPage1529-
dc.citation.endPage1538-
dc.identifier.bibliographicCitationNATURE GENETICS, Vol.49(10) : 1529-1538, 2017-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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