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An intragenic duplication in guanosine triphosphate cyclohydrolase-1 gene in a dopa-responsive dystonia family

Authors

  • Helen Ling MD,

    1. Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, London, United Kingdom
    2. Queen Square Brain Bank for Neurological Disorders and Institute of Neurology, University College London, London, United Kingdom
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    • Helen Ling and James M. Polke contributed equally to this article.

  • James M. Polke PhD,

    1. Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, London, United Kingdom
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    • Helen Ling and James M. Polke contributed equally to this article.

  • Mary G. Sweeney BSc,

    1. Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Andrea Haworth MSc,

    1. Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Catherine A. Sandford BSc,

    1. Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Simon J.R. Heales PhD,

    1. Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    2. Enzyme and Metabolic Unit, Great Ormond Street Hospital, London, United Kingdom
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  • Nicholas W. Wood PhD,

    1. Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Mary B. Davis PhD,

    1. Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Andrew J. Lees MD

    Corresponding author
    1. Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, London, United Kingdom
    2. Queen Square Brain Bank for Neurological Disorders and Institute of Neurology, University College London, London, United Kingdom
    • Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, UCL, 1 Wakefield Street, London, WC1N 1PJ, United Kingdom
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Abstract

Background:

Autosomal dominant dopa-responsive dystonia is commonly caused by mutations in the guanosine triphosphate cyclohydrolase-1 gene.

Methods:

We report a British family that has been followed for more than 20 years in which no mutations were previously identified.

Results:

Reanalysis of this pedigree detected a duplication of guanosine triphosphate cyclohydrolase-1 exon 2 in affected family members. mRNA analysis showed a mutant transcript with a tandem exon 2 duplication. Four family members developed dopa-responsive dystonia, with onset in their late teens, and subsequently developed restless leg syndrome and migraine.

Conclusions:

This is the first report of an intragenic guanosine triphosphate cyclohydrolase-1 duplication in a dopa-responsive dystonia family. © 2011 Movement Disorder Society

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