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De novo disruption of the proteasome regulatory subunit PSMD12 causes a syndromic neurodevelopmental disorder

dc.contributorPontificia Universidad Javeriana. Facultad de Medicina. Instituto de Genética Humana
dc.creatorKúry, Sébastien
dc.creatorBesnard, Thomas
dc.creatorEbstein, Frédéric
dc.creatorKhan, Tahir N.
dc.creatorGambin, Tomasz
dc.creatorDouglas, Jessica
dc.creatorBacino, Carlos A.
dc.creatorCraigen, William J.
dc.creatorSanders, Stephan J.
dc.creatorLehmann, Andrea
dc.creatorLatypova, Xénia
dc.creatorKhan, Kamal
dc.creatorPacault, Mathilde
dc.creatorSacharow, Stephanie
dc.creatorGlaser, Kimberly
dc.creatorBieth, Eric
dc.creatorPerrin-Sabourin, Laurence
dc.creatorJacquemont, Marie-Line
dc.creatorCho, Megan T.
dc.creatorRoeder, Elizabeth
dc.creatorDenommé-Pichon, Anne-Sophie
dc.creatorMonaghan, Kristin G.
dc.creatorYuan, Bo
dc.creatorXia, Fan
dc.creatorSylvain, Simon
dc.creatorBonneau, Dominique
dc.creatorParent, Philippe
dc.creatorGilbert-Dussardier, Brigitte
dc.creatorOdent, Sylvie
dc.creatorToutain, Annick
dc.creatorPasquier, Laurent
dc.creatorBarbouth, Deborah
dc.creatorShaw, Chad A.
dc.creatorPatel, Ankita
dc.creatorSmith, Janice L.
dc.creatorBi, Weimin
dc.creatorSchmitt, Sébastien
dc.creatorDeb, Wallid
dc.creatorNizon, Mathilde
dc.creatorMercier, Sandra
dc.creatorVincent, Marie
dc.creatorRooryck, Caroline
dc.creatorMalan, Valérrie
dc.creatorBriceño, Ignacio
dc.creatorGómez, Alberto
dc.creatorNugent, Kimberly M.
dc.creatorGibson, James B.
dc.creatorCogné, Benjamin
dc.creatorLupski, James R.
dc.creatorStessman, Holly A. F.
dc.creatorEichler, Evan E.
dc.creatorRetterer, Kyle
dc.creatorYang, Yaping
dc.creatorRedon, Richard
dc.creatorKatsanis, Nicholas
dc.creatorRosenfeld, Jill A.
dc.creatorKloetzel, Peter-Michael
dc.creatorGolzio, Christelle
dc.creatorBézieau, Stéphane
dc.creatorStankiewicz, Pawe
dc.creatorIsidor, Bertrand
dc.date2020-03-10T15:03:40Z
dc.date2020-04-15T13:32:04Z
dc.date2020-03-10T15:03:40Z
dc.date2020-04-15T13:32:04Z
dc.date2017-01-04
dc.date.accessioned2025-10-30T13:47:45Z
dc.date.available2025-10-30T13:47:45Z
dc.identifierhttps://www.cell.com/ajhg/fulltext/S0002-9297(17)30003-4
dc.identifier00029297 / 15376605 (Electrónico)
dc.identifierhttp://hdl.handle.net/10554/47557
dc.identifierhttps://doi.org/10.1016/j.ajhg.2017.01.003
dc.identifier.urihttp://test.repositoriodigital.com:8080/handle/123456789/188215
dc.descriptionQ1
dc.descriptionQ1
dc.descriptionReporte
dc.description352-363
dc.descriptionDegradation of proteins by the ubiquitin-proteasome system (UPS) is an essential biological process in the development of eukaryotic organisms. Dysregulation of this mechanism leads to numerous human neurodegenerative or neurodevelopmental disorders. Through a multi-center collaboration, we identified six de novo genomic deletions and four de novo point mutations involving PSMD12, encoding the non-ATPase subunit PSMD12 (aka RPN5) of the 19S regulator of 26S proteasome complex, in unrelated individuals with intellectual disability, congenital malformations, ophthalmologic anomalies, feeding difficulties, deafness, and subtle dysmorphic facial features. We observed reduced PSMD12 levels and an accumulation of ubiquitinated proteins without any impairment of proteasome catalytic activity. Our PSMD12 loss-of-function zebrafish CRISPR/Cas9 model exhibited microcephaly, decreased convolution of the renal tubules, and abnormal craniofacial morphology. Our data support the biological importance of PSMD12 as a scaffolding subunit in proteasome function during development and neurogenesis in particular; they enable the definition of a neurodevelopmental disorder due to PSMD12 variants, expanding the phenotypic spectrum of UPS-dependent disorders.
dc.formatPDF
dc.formatapplication/pdf
dc.formatPapel / Electrónico
dc.formatapplication/pdf
dc.languagespa
dc.rightsAtribución-NoComercial 4.0 Internacional
dc.rightshttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceAmerican Journal of Human Genetics; Vol. 100 Núm. 2 (2017)
dc.subjectPSMD12
dc.subjectIntellectual disability
dc.subjectProteasome 26S
dc.subjectRPN5
dc.subjectUbiquitin
dc.subjectSyndromic neurodevelopmental disorder
dc.titleDe novo disruption of the proteasome regulatory subunit PSMD12 causes a syndromic neurodevelopmental disorder
dc.typeinfo:eu-repo/semantics/article
dc.typehttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.typeArtículo de revista


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