Volume 11, Issue 9, Pages 764-773 (September 2012) Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study  Hendrik Rosewich, MD, Holger Thiele, MD, Andreas Ohlenbusch, PhD, Ulrike Maschke, MD, Janine Altmüller, MD, Peter Frommolt, PhD, Birgit Zirn, PhD, Friedrich Ebinger, MD, Prof Hartmut Siemes, MD, Prof Peter Nürnberg, PhD, Prof Knut Brockmann, MD, Prof Jutta Gärtner, MD  The Lancet Neurology  Volume 11, Issue 9, Pages 764-773 (September 2012) DOI: 10.1016/S1474-4422(12)70182-5 Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure Predicted locations of the ATP1A3 mutations in the Na+/K+ ATPase α3-subunit ATPase subunit α3.isoform 1 is the predominant splice variant of the α3-subunit. Missense mutations reported previously in patients with rapid-onset dystonia-parkinsonism are shown in blue.21–31 Missense mutations and one splice-site mutation found in patients with AHC, identified in this study, are shown in red. Various conserved functional ATP1A3 domains and transmembrane-regions are thus predicted to be affected by aminoacid changes. At three aminoacid positions (shown in bold) different non-synonymous aminoacid substitutions have been also reported in patients with rapid-onset dystonia-parkinsonism. The splice-site mutation 2542+1G>A is located at the boundary of intron 18 and presumably results in exon skipping. Cation ATPase N=cation transporter/ATPase, N-terminus. HAD-like=haloacid dehalogenase-like hydrolases. Cation ATPase C=cation transporting ATPase, C-terminus. ATPase-IIC X-K=Na+ or H+ efflux–K+ uptake antiporter, P-type ATPase, α-subunit. TMR=transmembrane-region. The Lancet Neurology 2012 11, 764-773DOI: (10.1016/S1474-4422(12)70182-5) Copyright © 2012 Elsevier Ltd Terms and Conditions