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dc.rights.licenseopenen_US
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorANGELINI, Chloe
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorDURAND, Christelle Marie
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorFERGELOT, Patricia
hal.structure.identifierService de génétique médicale
dc.contributor.authorDEFORGES, Julie
hal.structure.identifierService de pathologie [Bordeaux]
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
dc.contributor.authorVITAL, Anne
hal.structure.identifierDépartement de Neuro-Radiologie [Bordeaux] [DNR - Bordeaux]
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
dc.contributor.authorMENEGON, Patrice
dc.contributor.authorSARRAZIN, Elizabeth
dc.contributor.authorBELLANCE, Remi
dc.contributor.authorMATHIS, Stéphane
dc.contributor.authorGONZALEZ, Victoria
dc.contributor.authorRENAUD, Mathilde
dc.contributor.authorFRISMAND, Solène
dc.contributor.authorSCHMITT, Emmanuelle
dc.contributor.authorROUANET, Marie
dc.contributor.authorBURGLEN, Lydie
dc.contributor.authorCHABROL, Brigitte
dc.contributor.authorDESNOUS, Béatrice
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorARVEILER, Benoit
dc.contributor.authorSTEVANIN, Giovanni
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorCOUPRY, Isabelle
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorGOIZET, Cyril
dc.date.accessioned2024-02-16T09:45:03Z
dc.date.available2024-02-16T09:45:03Z
dc.date.issued2023-11-01
dc.identifier.issn1531-8257en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/188194
dc.description.abstractEnMitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by mutations in the C19orf12 gene. MPAN typically appears in the first two decades of life and presents with progressive dystonia-parkinsonism, lower motor neuron signs, optic atrophy, and abnormal iron deposits predominantly in the basal ganglia. MPAN, initially considered as a strictly autosomal recessive disease (AR), turned out to be also dominantly inherited (AD). Our aim was to better characterize the clinical, molecular, and functional spectra associated with such dominant pathogenic heterozygous C19orf12 variants. We collected clinical, imaging, and molecular information of eight individuals from four AD-MPAN families and obtained brain neuropathology results for one. Functional studies, focused on energy and iron metabolism, were conducted on fibroblasts from AD-MPAN patients, AR-MPAN patients, and controls. We identified four heterozygous C19orf12 variants in eight AD-MPAN patients. Two of them carrying the familial variant in mosaic displayed an atypical late-onset phenotype. Fibroblasts from AD-MPAN showed more severe alterations of iron storage metabolism and autophagy compared to AR-MPAN cells. Our data add strong evidence of the realness of AD-MPAN with identification of novel monoallelic C19orf12 variants, including at the mosaic state. This has implications in diagnosis procedures. We also expand the phenotypic spectrum of MPAN to late onset atypical presentations. Finally, we demonstrate for the first time more drastic abnormalities of iron metabolism and autophagy in AD-MPAN than in AR-MPAN.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enNBIA
dc.subject.enautosomal dominant MPAN
dc.subject.enC19orf12
dc.subject.enmosaicism
dc.subject.enlate-onset MPAN
dc.title.enAutosomal Dominant MPAN: Mosaicism Expands the Clinical Spectrum to Atypical Late-Onset Phenotypes.
dc.title.alternativeMov Disorden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1002/mds.29576en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed37605305en_US
bordeaux.journalMovement Disordersen_US
bordeaux.page2103-2115en_US
bordeaux.volume38en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDAgence de la Biomédecineen_US
bordeaux.import.sourcepubmed
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcepubmed
dc.rights.ccCC BY-NC-NDen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Movement%20Disorders&rft.date=2023-11-01&rft.volume=38&rft.issue=11&rft.spage=2103-2115&rft.epage=2103-2115&rft.eissn=1531-8257&rft.issn=1531-8257&rft.au=ANGELINI,%20Chloe&DURAND,%20Christelle%20Marie&FERGELOT,%20Patricia&DEFORGES,%20Julie&VITAL,%20Anne&rft.genre=article


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