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

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

Lazarov, Elinor
Max Planck Society;

Hillebrand, Merle
Max Planck Society;

Schröder, Simone
Max Planck Society;

Ternka, Katharina
Max Planck Society;

Hofhuis, Julia
Max Planck Society;

Ohlenbusch, Andreas
Max Planck Society;

Barrantes-Freer, Alonso
Max Planck Society;

Pardo, Luis A.
Max Planck Society;

Fruergaard, Marlene U.
Max Planck Society;

Nissen, Poul
Max Planck Society;

Brockmann, Knut
Max Planck Society;

Gärtner, Jutta
Max Planck Society;

Rosewich, Hendrik
Max Planck Society;

External Resource

http://www.sciencedirect.com/science/article/pii/S0969996120302874
(Any fulltext)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

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.

Cite as: https://hdl.handle.net/21.11116/0000-0009-F261-8

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.