A novel mutation in the ATP1A2 gene causes alternating hemiplegia of childhood

• Published in: Journal of medical genetics 2004-08, Vol.41 (8), p.621-628
• Main Authors: Bassi, M T, Bresolin, N, Tonelli, A, Nazos, K, Crippa, F, Baschirotto, C, Zucca, C, Bersano, A, Dolcetta, D, Boneschi, F M, Barone, V, Casari, G
• Format: Article
• Language: English
• Subjects: Adult; AHC; alternating hemiplegia; alternating hemiplegia of childhood; benign infantile convulsions; BFIC; Biological and medical sciences; Child; computed tomography; creatin kinase; DNA Mutational Analysis - methods; EEG; electroencephalography; epilepsy; familial hemiplegic migraine; Female; FHM; General aspects. Genetic counseling; Genes; Haplotypes; Haplotypes - genetics; Headaches; Hemiplegia - genetics; Hemiplegia - pathology; Humans; Hypotheses; IHC; international classification of headaches; K ATPase; Letter to JMG; Localization; magnetic resonance imaging; Male; Medical genetics; Medical sciences; Migraine; MRI; Mutation; Mutation, Missense - genetics; Paralysis; Pedigree; Phosphorylation; Plasma; Proteins; Sodium-Potassium-Exchanging ATPase - genetics; Sodium-Potassium-Exchanging ATPase - physiology
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2003.017863

Some of the aspects of AHC, however, are clearly distinct from FHM, including choreoathetosis, dystonic posturing, and a progressive course associated with mental deterioration. 7 Concerning the possible genetic origin of the disease, only a few familial cases have been described so far, providing evidence to support an autosomal dominant genetic mechanism of transmission. 8, 9 In the first AHC family described, a balanced reciprocal translocation was detected: 46,XY, t(3;9)(p26;q34), thus indicating the first two genomic regions possibly associated with the disease. 8 Subsequently, mitochondrial abnormalities identified in a few sporadic AHC patients suggested the hypothesis, which was however never clearly confirmed, of a mitochondrial dysfunction underlying the pathogenesis of the disease. 10 Key points Alternating hemiplegia of childhood (AHC, MIM 104290) is a rare syndrome, characterised by early onset of episodic hemi- or quadriplegia lasting minutes to days. [...]the AHC mutation involves a highly conserved sequence, DKTGTL, which is the target of the β-aspartyl-phosphorylation reaction during catalysis in all P-type E1-E2-ATPases independently of their cation specificities. 16, 17 According to this, the AHC mutation appears to cause a loss of function effect when transfected in HeLa cells, despite its correct localisation in the plasma membrane.