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Novel splice site CACNA1A mutation causing episodic ataxia type 2

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Abstract.

Episodic ataxia type 2 (EA-2) is an autosomal dominant neurological disorder, characterized by episodes of ataxia, vertigo, nausea, nystagmus, and fatigue, associated with acetazolamide responsiveness. The disease is caused by mutations in the P/Q-type calcium channel Cav2.1 subunit gene, CACNA1A, located on chromosome 19p13.2. We analyzed a family with 13 affected individuals for linkage to this locus and reached a two-point maximum LOD score of 4.48. A novel CACNA1A mutation, IVS36–2A>G, at the 3′ acceptor splice site of intron 36 was identified by sequencing. It is the first described CACNA1A acceptor splice site mutation and the most C-terminal EA-2-causing mutation reported to date.

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Acknowledgements.

This study was supported by funding from the Helsinki University Central Hospital, the Research Foundation of the University of Helsinki (Young Scientist’s Award), the Biomedicum Helsinki Foundation, the Finnish Cultural Foundation, National Institutes of Health (RO1 NS37675–02 to A.P.), the Orion Research Corporation, and the Finnish Neurology Foundation. The authors would like to thank the EA-2 family members for their devoted participation.

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Authors and Affiliations

  1. Biomedicum Helsinki, Molecular Medicine Research Program, University of Helsinki, Helsinki, Finland

    M. A. Kaunisto, R. Sallinen, E. Hämäläinen, A. Palotie & M. Wessman

  2. Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland

    M. A. Kaunisto, R. Sallinen, A. Orpana, A. Palotie & M. Wessman

  3. Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland

    H. Harno, M. Kallela, H. Somer & M. Färkkilä

  4. Laboratory of Helsinki University Central Hospital, Helsinki, Finland

    E. Hämäläinen, A. Orpana & A. Palotie

  5. Biomedicum Helsinki, Program for Developmental and Reproductive Biology and Haartman Institute, University of Helsinki, Helsinki, Finland

    P.J. Miettinen

  6. Hospital for Sick Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland

    P.J. Miettinen

  7. Department of Pathology and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

    J. Vesa & A. Palotie

  8. The Finnish Genome Center, University of Helsinki, Helsinki, Finland

    A. Palotie

  9. Folhälsan Research Center, Helsinki, Finland

    M. Wessman

  10. Biomedicum Helsinki, Molecular Medicine Research Program, Room B326b, P.O. Box 700, 00029 HUS, Finland

    M. Wessman

Authors
  1. M. A. Kaunisto
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  2. H. Harno
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  3. M. Kallela
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  4. H. Somer
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  5. R. Sallinen
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  6. E. Hämäläinen
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  7. P.J. Miettinen
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  8. J. Vesa
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  9. A. Orpana
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  10. A. Palotie
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  11. M. Färkkilä
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  12. M. Wessman
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Corresponding author

Correspondence to M. Wessman.

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Kaunisto, M.A., Harno, H., Kallela, M. et al. Novel splice site CACNA1A mutation causing episodic ataxia type 2. Neurogenetics 5, 69–73 (2004). https://doi.org/10.1007/s10048-003-0161-0

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  • DOI: https://doi.org/10.1007/s10048-003-0161-0

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