Epilepsy as part of the phenotype associated with ATP1A2 mutations

Authors

  • Liesbet Deprez,

    1. Neurogenetics Group, Department of Molecular Genetics, VIB; Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge; Antwerpen, Belgium
    3. University of Antwerp, Antwerpen, Belgium
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  • Sarah Weckhuysen,

    1. Department of Neurology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
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  • Katelijne Peeters,

    1. Department of Neurology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
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  • Tine Deconinck,

    1. Neurogenetics Group, Department of Molecular Genetics, VIB; Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge; Antwerpen, Belgium
    3. University of Antwerp, Antwerpen, Belgium
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  • Kristl G. Claeys,

    1. Neurogenetics Group, Department of Molecular Genetics, VIB; Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge; Antwerpen, Belgium
    3. Division of Neurology, University Hospital of Antwerp, Antwerpen, Belgium
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  • Lieve R.F. Claes,

    1. Neurogenetics Group, Department of Molecular Genetics, VIB; Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge; Antwerpen, Belgium
    3. University of Antwerp, Antwerpen, Belgium
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  • Arvid Suls,

    1. Neurogenetics Group, Department of Molecular Genetics, VIB; Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge; Antwerpen, Belgium
    3. University of Antwerp, Antwerpen, Belgium
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  • Tine Van Dyck,

    1. Neurogenetics Group, Department of Molecular Genetics, VIB; Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge; Antwerpen, Belgium
    3. University of Antwerp, Antwerpen, Belgium
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  • André Palmini,

    1. Division of Neurology & Porte Alegre Epilepsy Surgery Program, Faculty of Medicine & Hospital São Lucas, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil
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  • Gert Matthijs,

    1. Center for Human Genetics, University of Leuven, Leuven, Belgium
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  • Wim Van Paesschen,

    1. Department of Neurology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
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  • Peter De Jonghe

    1. Neurogenetics Group, Department of Molecular Genetics, VIB; Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge; Antwerpen, Belgium
    3. University of Antwerp, Antwerpen, Belgium
    4. Division of Neurology, University Hospital of Antwerp, Antwerpen, Belgium
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  • Liesbet Deprez, Katelijne, and Sarah Weckhuysen contributed equally to this work, and Wim Van Paesscheu and Peter De Jonghe contributed equally to this work.

Address correspondence to Prof. Dr. P. De Jonghe, Neurogenetics Research Group, Department of Molecular Genetics, VIB, University of Antwerp–CDE, Universiteitsplein 1, BE-2610 Antwerpen, Belgium. E-mail: peter.dejonghe@ua.ac.be

Summary

Purpose: Mutations in the ATP1A2 gene have been described in families with familial hemiplegic migraine (FHM). FHM is a variant of migraine with aura characterized by the occurrence of hemiplegia during the aura. Within several FHM families, some patients also had epileptic seizures. In this study we tested the hypothesis that mutations in ATP1A2 may be common in patients presenting with epilepsy and migraine.

Methods: We selected 20 families with epilepsy and migraine and performed mutation analysis of ATP1A2 in the probands by direct sequencing of all exons and splice-site junctions.

Results: Novel ATP1A2 mutations were found in two of the 20 families (10%). The p.Gly900Arg mutation was present in a family with epilepsy and FHM, and the p.Cys702Tyr mutation occurred in a family with occipitotemporal epilepsy and migraine with and without visual aura. In the two families together, six mutation carriers had the combination of epilepsy and migraine, two had only epilepsy, and six had only migraine.

Discussion: This study shows that a history of migraine and a family history of both epilepsy and migraine should be obtained in all patients presenting with epilepsy in the epilepsy clinic. It may be worthwhile to screen patients with a combination of epilepsy and migraine and a positive family history of either migraine or epilepsy for mutations in the ATP1A2 gene.

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