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Comparative analysis of alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism ATP1A3 mutations reveals functional deficits, which do not correlate with disease severity

dc.contributor.authorLazarov, Elinor
dc.contributor.authorHillebrand, Merle
dc.contributor.authorSchröder, Simone
dc.contributor.authorTernka, Katharina
dc.contributor.authorHofhuis, Julia
dc.contributor.authorOhlenbusch, Andreas
dc.contributor.authorBarrantes-Freer, Alonso
dc.contributor.authorPardo, Luis A.
dc.contributor.authorFruergaard, Marlene U.
dc.contributor.authorNissen, Poul
dc.contributor.authorBrockmann, Knut
dc.contributor.authorGärtner, Jutta
dc.contributor.authorRosewich, Hendrik
dc.date.accessioned2020-07-31T15:21:57Z
dc.date.available2020-07-31T15:21:57Z
dc.date.issued2020de
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/17488
dc.description.abstractHeterozygous mutations in the ATP1A3 gene, coding for an alpha subunit isoform (α3) of Na$^+$/K$^+$-ATPase, are the primary genetic cause for rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). Recently, cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS), early infantile epileptic encephalopathy (EIEE), childhood rapid onset ataxia (CROA) and relapsing encephalopathy with rapid onset ataxia (RECA) extend the clinical spectrum of ATP1A3 related disorders. AHC and RDP demonstrate distinct clinical features, with AHC symptoms being generally more severe compared to RDP. Currently, it is largely unknown what determines the disease severity, and whether severity is linked to the degree of functional impairment of the α3 subunit. Here we compared the effect of twelve different RDP and AHC specific mutations on the expression and function of the α3 Na$^+$/K$^+$-ATPase in transfected HEK cells and oocytes. All studied mutations led to functional impairment of the pump, as reflected by lower survival rate and reduced pump current. No difference in the extent of impairment, nor in the expression level, was found between the two phenotypes, suggesting that these measures of pump dysfunction do not exclusively determine the disease severity.de
dc.description.sponsorshipOpen-Access-Publikationsfonds 2020
dc.language.isoengde
dc.rightsopenAccess
dc.rightsNamensnennung 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectParkinsonism; Alternating hemiplegia of childhood; AHC; Rapid-onset dystonia-parkinsonism; RDP; ATP1A3; P-type ATPase; Na+/K+-ATPase alpha 3 subunit; Movement disorderde
dc.subject.ddc610
dc.titleComparative analysis of alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism ATP1A3 mutations reveals functional deficits, which do not correlate with disease severityde
dc.typejournalArticlede
dc.identifier.doi10.1016/j.nbd.2020.105012
dc.type.versionpublishedVersionde
dc.relation.pISSN09699961
dc.bibliographicCitation.volume143de
dc.bibliographicCitation.firstPage1de
dc.bibliographicCitation.lastPage9de
dc.type.subtypejournalArticle
dc.bibliographicCitation.articlenumber105012de
dc.description.statuspeerReviewedde
dc.bibliographicCitation.journalNeurobiology of Diseasede


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