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

Lazarov, Elinor; Hillebrand, Merle; Schröder, Simone; Ternka, Katharina; Hofhuis, Julia; Ohlenbusch, Andreas; Barrantes-Freer, Alonso; Pardo, Luis A.; Fruergaard, Marlene U.; Nissen, Poul; Brockmann, Knut; Gärtner, Jutta; Rosewich, Hendrik

doi:10.1016/j.nbd.2020.105012

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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

Lazarov, E., Hillebrand, M., Schröder, S., Ternka, K., Hofhuis, J., Ohlenbusch, A., et al. (2020). Comparative analysis of alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism ATP1A3 mutations reveals functional deficits, which do not correlate with disease severity. Neurobiology of Disease, 143, 105012. doi:10.1016/j.nbd.2020.105012.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0009-F261-8 Version Permalink: https://hdl.handle.net/21.11116/0000-0009-F262-7

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http://www.sciencedirect.com/science/article/pii/S0969996120302874 (Any fulltext) Open Access status unknown

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Lazarov, Elinor¹, Author
Hillebrand, Merle¹, Author
Schröder, Simone¹, Author
Ternka, Katharina¹, Author
Hofhuis, Julia¹, Author
Ohlenbusch, Andreas¹, Author
Barrantes-Freer, Alonso¹, Author
Pardo, Luis A.¹, Author
Fruergaard, Marlene U.¹, Author
Nissen, Poul¹, Author
Brockmann, Knut¹, Author
Gärtner, Jutta¹, Author
Rosewich, Hendrik¹, Author

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1Max Planck Society, ou_persistent13

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Free keywords: Parkinsonism Alternating hemiplegia of childhood AHC Rapid-onset dystonia-parkinsonism RDP ATP1A3 P-type ATPase Na/K-ATPase alpha 3 subunit Movement disorder

Abstract: Heterozygous 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. GenBank RefSeq accession numbers: ATP1A3: NM_152296.4; ATP1B1: NM_001677.3.

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Dates: Published Online: 2020-07-10Date issued: 2020-07-13

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Identifiers: Other: 32653672
DOI: 10.1016/j.nbd.2020.105012
ISSN: 0969-9961

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Title: Neurobiology of Disease

Source Genre: Journal

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Pages: - Volume / Issue: 143 Sequence Number: - Start / End Page: 105012 Identifier: -