Screening of mutations in GNAL in sporadic dystonia patients

Authors

  • Claudia Dufke PhD,

    1. Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University of Tuebingen, Tuebingen, Germany
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  • Marc Sturm PhD,

    1. Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University of Tuebingen, Tuebingen, Germany
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  • Christopher Schroeder MD,

    1. Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University of Tuebingen, Tuebingen, Germany
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  • Susanne Moll,

    1. Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University of Tuebingen, Tuebingen, Germany
    2. Transgenic Facility Tuebingen, University of Tuebingen, Tuebingen, Germany
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  • Thomas Ott PhD,

    1. Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University of Tuebingen, Tuebingen, Germany
    2. Transgenic Facility Tuebingen, University of Tuebingen, Tuebingen, Germany
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  • Olaf Riess MD,

    1. Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University of Tuebingen, Tuebingen, Germany
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  • Peter Bauer MD,

    1. Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University of Tuebingen, Tuebingen, Germany
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  • Kathrin Grundmann MD

    Corresponding author
    1. Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University of Tuebingen, Tuebingen, Germany
    • Correspondence to: Dr. Kathrin Grundmann-Hauser, Institute of Medical Genetics and Applied Genomics, Rare Disease Center Tuebingen, University Tuebingen, Calwerstrasse 7, 72076 Tuebingen, Germany; kathrin.grundmann@med.uni-tuebingen.de

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  • Funding agencies: Kathrin Grundmann was funded by the Deutsche Forschungsgemeinschaft, the IZKF of the University of Tuebingen, and the Elitepostdoc Programme Baden Württemberg

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Background

GNAL mutations have been shown to cause adult-onset isolated dystonia, a disabling movement disorder characterized by involuntary muscle contractions causing twisting and repetitive movements or abnormal postures.

Methods

To test the frequency of GNAL mutations in a series of 137 German patients with sporadic dystonia patients we used next-generation sequencing of amplicon-derived barcoded NexteraXT libraries for the coding exons and adjacent intronic sequences of GNAL.

Results

In our cohort we identified 1 pathogenic nonsense mutation (c.733C>T, p.R245*) in a patient with cervical dystonia. In a second patient a synonymous coding nonsynonymous variant (c.G252A, p.E84E) was detected, which is predicted to alter a splice site.

Conclusions

Our findings further support GNAL as causative gene in adult-onset isolated dystonia. © 2014 International Parkinson and Movement Disorder Society

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