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article, pubmed, google, scholar, cas, epilepsy, scna, mutations, ataxia, episodic, neurology, seizures, mutation, channel, research, sodium, gene, lerche, epilepsia, central, tübingen, access, brain, clinical, novo, neurosci, neurol, university, germany, privacy, cookies, content, journal, neonatal, maljevic, biskup, neonatalinfantile, patients, epileptic, familial, helsinki, data, publish, search, phenotype, spectrum, open, disorders, syndrome, doijx,

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month download article/chapter calcium-sensitive potassium channelopathy voltage-gated sodium channels scn2a-related epileptic encephalopathies late-onset episodic ataxia neonatal-onset seizures remitting inherited neonatal-infantile epilepsy early-onset absence epilepsy benign infantile seizures familial infantile seizures sodium channel blockers full article pdf onset episodic ataxia episodic neurologic disorders na+ current density george al jr privacy choices/manage cookies voltage-dependent inactivation related subjects exome sequencing identifies severe intellectual disability clinical brain research change channel gating epileptic disorders 16 epileptic disorders primary episodic ataxias german research foundation folkhälsan research foundation research programs unit de novo mutations age-dependent seizures sodium channelopathy idiopathic generalized epilepsy cell patch-clamping cervantes-barragan de scn2a gene european economic area scope submit manuscript experience repeated episodes nerve excitability studies wong-kisiel lc 11th european congress european science foundation hoppe-seyler-str ethics declarations conflicts article journal causative scn2a mutations scn2a mutations expanding conditions privacy policy ann-liz träskelin

Questions {❓}

• Berg AT, Plioplys S (2012) Epilepsy and autism: is there a special relationship?
• Kasteleijn-Nolst Trenite D, Parisi P (2012) Migraine in the borderland of epilepsy: “migralepsy” an overlapping syndrome of children and adults?

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         headline:Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia
         description:Mutations in SCN2A cause epilepsy syndromes of variable severity including neonatal-infantile seizures. In one case, we previously described additional childhood-onset episodic ataxia. Here, we corroborate and detail the latter phenotype in three further cases. We describe the clinical characteristics, identify the causative SCN2A mutations and determine their functional consequences using whole-cell patch-clamping in mammalian cells. In total, four probands presented with neonatal-onset seizures remitting after five to 13 months. In early childhood, they started to experience repeated episodes of ataxia, accompanied in part by headache or back pain lasting minutes to several hours. In two of the new cases, we detected the novel mutation p.Arg1882Gly. While this mutation occurred de novo in both patients, one of them carries an additional known variant on the same SCN2A allele, inherited from the unaffected father (p.Gly1522Ala). Whereas p.Arg1882Gly alone shifted the activation curve by −4 mV, the combination of both variants did not affect activation, but caused a depolarizing shift of voltage-dependent inactivation, and a significant increase in Na+ current density and protein production. p.Gly1522Ala alone did not change channel gating. The third new proband carries the same de novo SCN2A gain-of-function mutation as our first published case (p.Ala263Val). Our findings broaden the clinical spectrum observed with SCN2A gain-of-function mutations, showing that fairly different biophysical mechanisms can cause a convergent clinical phenotype of neonatal seizures and later onset episodic ataxia.
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            name:University of Helsinki
            address:
               name:Folkhälsan Institute of Genetics, Neuroscience Center and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland
               type:PostalAddress
            type:Organization
      name:B. A. Neubauer
      affiliation:
            name:University Medical Clinic Giessen
            address:
               name:Department of Neuropediatrics, University Medical Clinic Giessen, Giessen, Germany
               type:PostalAddress
            type:Organization
      name:H. Lerche
      affiliation:
            name:University of Tübingen
            address:
               name:Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:U. B. S. Hedrich
      affiliation:
            name:University of Tübingen
            address:
               name:Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
      name:Department of Neuropediatrics, University Medical Clinic Giessen, Giessen, Germany
      name:Epilepsy Center Kork, Kehl-Kork, Germany
      name:Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
      name:Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
      name:Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
      name:Department of Pediatric Neurology, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
      name:CeGaT GmbH, University of Tübingen, Tübingen, Germany
      name:CeGaT GmbH, University of Tübingen, Tübingen, Germany
      name:Department of Neurology with focus on Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
      name:German Center for Neurodegenerative Diseases (DZNE) Tübingen, Tübingen, Germany
      name:Folkhälsan Institute of Genetics, Neuroscience Center and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland
      name:Folkhälsan Institute of Genetics, Neuroscience Center and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland
      name:Department of Neuropediatrics, University Medical Clinic Giessen, Giessen, Germany
      name:Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
      name:Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
WebPageElement:
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      cssSelector:.main-content

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