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Novel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotype

2020Journal article Open access
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dc.contributor.authorSantos, Mariana
dc.contributor.authorDamásio, Joana
dc.contributor.authorKun-Rodrigues, Celia
dc.contributor.authorBarbot, Clara
dc.contributor.authorSequeiros, Jorge
dc.contributor.authorBrás, José
dc.contributor.authorAlonso, Isabel
dc.contributor.authorGuerreiro, Rita
dc.date.accessioned2022-01-11T16:41:31Z
dc.date.available2022-01-11T16:41:31Z
dc.date.issued2020
dc.description.abstractHomozygous variants in MAG, encoding myelin-associated glycoprotein (MAG), have been associated with complicated forms of hereditary spastic paraplegia (HSP). MAG is a glycoprotein member of the immunoglobulin superfamily, expressed by myelination cells. In this study, we identified a novel homozygous missense variant in MAG (c.124T>C; p.Cys42Arg) in a Portuguese family with early-onset autosomal recessive cerebellar ataxia with neuropathy and oculomotor apraxia. We used homozygosity mapping and exome sequencing to identify the MAG variant, and cellular studies to confirm its detrimental effect. Our results showed that this variant reduces protein stability and impairs the post-translational processing (N-linked glycosylation) and subcellular localization of MAG, thereby associating a loss of protein function with the phenotype. Therefore, MAG variants should be considered in the diagnosis of hereditary cerebellar ataxia with oculomotor apraxia, in addition to spastic paraplegia.pt_PT
dc.description.sponsorshipThis work was funded by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P.,under the project UIDB/04293/2020. It was also funded by FEDER funds through the Programa OperacionalFactores de Competitividade—COMPETE 2020 and by Nacional funds through the FCT [COMPETE:POCI-01-0145-FEDER-007440]. This work was also funded in part by the FCT grant FCT-ANR/BEX-GMG/0008/2013and the Porto Neurosciences and Neurologic Disease Research Initiative at the i3S (Norte-01-0145-FEDER-000008),supported by Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020Partnership Agreement, also through FEDER. The authors also acknowledge the support of the i3S ScientificPlatform Advanced Light Microscopy, member of the PPBI (PPBI-POCI-01-0145-FEDER-022122) and GenomePT(POCI-01-0145-FEDER-022184). MS was the recipient of a fellowship (SFRH/BPD/116046/2016) from the FCTsupported by POPH/MCTES funding.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSantos M, Damásio J, Kun-Rodrigues C, et al. Novel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotype. J Clin Med. 2020;9(4):1212. Published 2020 Apr 23. doi:10.3390/jcm9041212pt_PT
dc.identifier.doi10.3390/jcm9041212pt_PT
dc.identifier.issn2077-0383
dc.identifier.urihttp://hdl.handle.net/10400.16/2659
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2077-0383/9/4/1212pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectcerebellar ataxiapt_PT
dc.subjectexome sequencingpt_PT
dc.subjectmyelin-associated glycoproteinpt_PT
dc.titleNovel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotypept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceSwitzerlandpt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage1212pt_PT
oaire.citation.titleJournal of Clinical Medicinept_PT
oaire.citation.volume9pt_PT
person.familyNameSantos
person.familyNameDamásio
person.familyNameKun-Rodrigues
person.familyNameSequeiros
person.familyNameGuerreiro
person.givenNameMariana
person.givenNameJoana
person.givenNameCelia
person.givenNameJorge
person.givenNameRita
person.identifier666710
person.identifier.ciencia-id701A-EB83-4699
person.identifier.ciencia-id8917-86CE-D005
person.identifier.ciencia-id0E17-D288-38BC
person.identifier.ciencia-idDC16-E70B-5CF7
person.identifier.orcid0000-0002-2343-2215
person.identifier.orcid0000-0002-6539-6398
person.identifier.orcid0000-0003-4528-0061
person.identifier.orcid0000-0002-9846-1037
person.identifier.orcid0000-0001-5879-3486
person.identifier.scopus-author-id56406800400
person.identifier.scopus-author-id7005499969
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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