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Autosomal Dominant MPAN: Mosaicism Expands the Clinical Spectrum to Atypical Late-Onset Phenotypes

dc.rights.licenseopenen_US
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorANGELINI, Chloe
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
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
dc.contributor.authorDEFORGES, Julie
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorVITAL, Anne
dc.contributor.authorMENEGON, Patrice
dc.contributor.authorSARRAZIN, Elizabeth
dc.contributor.authorBELLANCE, Remi
dc.contributor.authorMATHIS, Stephane
dc.contributor.authorGONZALEZ, Victoria
dc.contributor.authorRENAUD, Mathilde
dc.contributor.authorFRISMAND, Solene
dc.contributor.authorSCHMITT, Emmanuelle
dc.contributor.authorROUANET, Marie
dc.contributor.authorBURGLEN, Lydie
dc.contributor.authorCHABROL, Brigitte
dc.contributor.authorDESNOUS, Beatrice
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorARVEILER, Benoit
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorSTEVANIN, Giovanni
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorCOUPRY, Isabelle
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorGOIZET, Cyril
dc.date.accessioned2024-04-29T10:18:33Z
dc.date.available2024-04-29T10:18:33Z
dc.date.issued2023-08-21
dc.identifier.issn1531-8257en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/199364
dc.description.abstractEnBackground: Mitochondrial 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). Objectives: Our aim was to better characterize the clinical, molecular, and functional spectra associated with such dominant pathogenic heterozygous C19orf12 variants. Methods: 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. Results: 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. Conclusion: 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. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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.enC19orf12
dc.subject.enNBIA
dc.subject.enautosomal dominant MPAN
dc.subject.enlate-onset MPAN
dc.subject.enmosaicism
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]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed37605305en_US
bordeaux.journalMovement disordersen_US
bordeaux.page2103-2115en_US
bordeaux.volume38en_US
bordeaux.hal.laboratoriesInstitut de neurosciences cognitives et intégratives d'Aquitaine (INCIA) - UMR 5287en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDAgence de la Biomédecineen_US
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
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=2023-08-21&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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