Lifetime information allowed us to investigate whether a sign/symptom was present previously, even if it was no longer present at the time of inclusion or at 6–12 years old. [ojrd.biomedcentral.com]

We carried out mapping of the variants discussed in the present review. [frontiersin.org]

A novel ATP1A3 mutation with unique clinical presentation. J Neurol Sci. 2014a;341:133–5. [ncbi.nlm.nih.gov]

• Movement Disorder

  Fox Foundation, Movement Disorders Society, NIH/NINDS, Parkinson Study Group, Sunovion, but has no owner interest in any pharmaceutical company. [frontiersin.org]

  Roubergue A, Roze E, Vuillaumier-Barrot S, Fontenille MJ, Meneret A, et al. (2013) The multiple faces of the ATP1A3-related dystonic movement disorder. Mov Disord 28: 1457–1459. View Article Google Scholar 4. [journals.plos.org]

  The majority of patients with either of the three most frequent mutations presented movement disorders over their lifetime; 72–89 % presented movement disorders between 6 and 12 years of age. [ojrd.biomedcentral.com]

  The multiple faces of the ATP1A3-related dystonic movement disorder. Mov Disord. 2013;28:1457–9. [PubMed: 23483595] Sarma AK, Khandker N, Kurczewski L, Brophy GM. Medical management of epileptic seizures: challenges and solutions. [ncbi.nlm.nih.gov]

• Cerebral Palsy

  Dopa-responsive dystonia simulating cerebral palsy. Pediatr. Neurol. 1994;11:236–40. [PubMed: 7880338] Oblak AL, Hagen MC, Sweadner KJ, Haq I, Whitlow CT, Maldjian JA, Epperson F, Cook JF, Stacy M, Murrell JR, Ozelius LJ, Brashear A, Ghetti B. [ncbi.nlm.nih.gov]

  Cerebral Palsy/Spastic Paraparesis Calame et al. described four non-relatives ATP1A3 p.Pro775Leu carriers, presenting spastic diplegia, developmental delay, epilepsy, and episodic neurological deterioration. [frontiersin.org]

• Weakness

  For example, AHC typically evolve with paroxysmal attacks of weakness. On the other end, RDP evolve usually with no paroxysms and a stationary evolution. [frontiersin.org]

  Fever-induced paroxysmal weakness and encephalopathy, a new phenotype of ATP1A3 mutation. Pediatr Neurol. 2017;73:101–5. [ncbi.nlm.nih.gov]

• Fever

  At age 6 years after a fever she developed marked and persisting visual impairment. [frontiersin.org]

  Fever-induced paroxysmal weakness and encephalopathy, a new phenotype of ATP1A3 mutation. Pediatr Neurol. 2017;73:101–5. [ncbi.nlm.nih.gov]

• Hearing Impairment

  At the age of 12 year old her examination revealed marked dysarthria, bradykinesia, ataxia of gait, muscular hypotonia, mild limbs dystonia, areflexia, optic atrophy, and cochlear hearing impairment (45). [frontiersin.org]

• Dystonia

  Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28:863–73. [ncbi.nlm.nih.gov]

  […] upper limb dystonia (42); and (4) slight focal hand dystonia-myoclonus (42). [frontiersin.org]

  Rapid-onset dystonia parkinsonism. Neurology. 1993;43:2596–602. Article CAS PubMed Google Scholar Brashear A, DeLeon D, Bressman SB, Thyagarajan D, Farlow MR, Dobyns WB. Rapid-onset dystonia-parkinsonism in a second family. [ojrd.biomedcentral.com]

  The mother had onset of eye deviation and dystonia at six months. She developed alternating episodes of hemiplegia at one year of age with or without eye deviation and dystonia, at the frequency of once per month, lasting about one hour per episode. [journals.plos.org]

• Ataxia

  ROA, rapid onset cerebellar ataxia; SPCA, slowly progressive cerebellar ataxia. [frontiersin.org]

  Beyond dystonia-parkinsonism: chorea and ataxia with ATP1A3 mutations. Mov Disord Clin Pract. 2016;3:402–4. [ncbi.nlm.nih.gov]

  CAPOS syndrome is characterized by an early-childhood onset of recurrent episodes of acute ataxia associated with febrile illnesses. [ojrd.biomedcentral.com]

  […] isolation, (5) immediate disappearance of all symptoms upon sleep, with probable recurrence of long-lasting bouts 10–20 min after awakening, (6) evidence of developmental delay, mental retardation, neurologic abnormalities, choreoathetosis and dystonia or ataxia [journals.plos.org]

• Areflexia

  RDP, rapid-onset dystonia-parkinsonism; AHC, alternating hemiplegia of childhood; CAPOS, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss; CAOS, cerebellar ataxia, areflexia, optic atrophy, and sensorineural hearing [frontiersin.org]

  CAOS-episodic cerebellar ataxia, areflexia, optic atrophy, and sensorineural hearing loss: a third allelic disorder of the ATP1A3 gene. J Child Neurol. 2015;30:1749–56. [ncbi.nlm.nih.gov]

  These acute episodes tend to decrease with time, but the neurologic sequelae are permanent and progressive, resulting in gait and limb ataxia and areflexia. [ojrd.biomedcentral.com]

• Cerebellar Ataxia

  ROA, rapid onset cerebellar ataxia; SPCA, slowly progressive cerebellar ataxia. [frontiersin.org]

  Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation. Dev Med Child Neurol. 2015;57:1183–6. [ncbi.nlm.nih.gov]

  Mutations in the ATP1A3 gene, are also found in patients with dystonia 12 (rapid-onset dystonia parkinsonism; RDP, MIM 128235) [24–27] and CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss, MIM 601338) syndrome [ojrd.biomedcentral.com]

• Convulsions

  Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Ann Neurol. 2003;54:360–6. [ncbi.nlm.nih.gov]

  One case had dystonia, while another had self-limited episodes of hypotonus, convergent strabismus, and febrile convulsions. [frontiersin.org]

Alternating hemiplegia of childhood: a study of 10 patients and results of flunarizine treatment. Neurology. 1993;43:36–41. [ncbi.nlm.nih.gov]

Neville BG, Ninan M (2007) The treatment and management of alternating hemiplegia of childhood. Dev Med Child Neurol 49: 777–780. View Article Google Scholar 2. [journals.plos.org]

Of these, p.Glu815Lys was associated with a severe phenotype, with more severe intellectual and motor disability. p.Asp801Asn appeared to confer a milder phenotypic expression, and p.Gly947Arg appeared to correlate with the most favourable prognosis, [ojrd.biomedcentral.com]

[…] of the disease, and p.Gly947Arg (8–15% of cases) has a favorable prognosis (33). [frontiersin.org]

An extensive survey of the molecular features of the mutations may shed light on the etiology of diseases and be useful for predicting the pathogenicity of novel ATP1A3 variants. [journals.plos.org]

A C-terminal mutation of ATP1A3 underscores the crucial role of sodium affinity in the pathophysiology of rapid-onset dystonia-parkinsonism. Hum Mol Genet. 2009;18:2370–7. [ncbi.nlm.nih.gov]

Weigand and colleagues [46] initially suggested that binding of the α3 subunit to ouabain may play a possible pathophysiological role. [ojrd.biomedcentral.com]

Consequently, the CAPOS mutant pump may fail to clear the neuron fast enough of the accumulated Na+ in relation to action potentials, and this defect might be part of the pathophysiological mechanism (41). [frontiersin.org]

The mutation D801N, demonstrated by Heinzen et al. [2], apparently prevents the binding of K+ at E2 conformation. But other variants are not so close to the ion binding site and their influences on protein functions remain unclear. [journals.plos.org]

However, unlike the p.Asp801Asn mutation, both the p.Glu815Lys and p.Gly947Arg mutations prevent binding of the α3 subunit to ouabain, yet these latter mutations, according to our results, were associated with very different phenotypes. [ojrd.biomedcentral.com]