Clinico-genetic comparisons of paroxysmal kinesigenic dyskinesia patients with and without PRRT2 mutations

Authors

  • L. C. S. Tan,

    Corresponding author
    1. Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute, Singapore City, Singapore
    2. Department of Neurology, National Neuroscience Institute, Singapore City, Singapore
    • Correspondence: L. C. S. Tan, Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore (tel.: (65) 6357 7171; fax: (65) 6357 7137; e-mail: louis_tan@nni.com.sg).

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  • K. Methawasin,

    1. Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute, Singapore City, Singapore
    2. Department of Neurology, National Neuroscience Institute, Singapore City, Singapore
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  • E. W. L. Teng,

    1. Department of Neurology, National Neuroscience Institute, Singapore City, Singapore
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  • A. R. J. Ng,

    1. Department of Neurology, National Neuroscience Institute, Singapore City, Singapore
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  • S. H. Seah,

    1. Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute, Singapore City, Singapore
    2. Department of Neurology, National Neuroscience Institute, Singapore City, Singapore
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  • W. L. Au,

    1. Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute, Singapore City, Singapore
    2. Department of Neurology, National Neuroscience Institute, Singapore City, Singapore
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  • J. J. Liu,

    1. Human Genetics, Genome Institute of Singapore, A*STAR, Singapore City, Singapore
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  • J. N. Foo,

    1. Human Genetics, Genome Institute of Singapore, A*STAR, Singapore City, Singapore
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  • Y. Zhao,

    1. Department of Clinical Research, Singapore General Hospital, Singapore City, Singapore
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  • E. K. Tan

    1. Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute, Singapore City, Singapore
    2. Department of Neurology, National Neuroscience Institute, Singapore City, Singapore
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Abstract

Background and purpose

Mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesias (PKD); however, not many detailed clinico-genetic correlations have been performed.

Methods

To investigate PRRT2 mutations in a mixed Asian PKD population and perform clinico-genetic correlations, we recruited patients between 2002 and 2011 and administered a standardized questionnaire.

Results

Amongst 29 unrelated patients with PKD recruited, five PRRT2 mutations were present in 15 patients. Three mutations (c.649dupC, c.649delC, c.649C>T) were previous reported, while three were novel mutations (c.604delT; c.609_611delACC/p.Ser202Hisfs; c.697_698delAG/p.Ser233Trp fsX5). Clinico-genetic correlations revealed that a history of seizures was more common in patients with PRRT2 mutations, although this did not reach statistical significance (P= 0.08). A younger age of onset, non-Chinese, and the presence of premonitory sensations were significantly associated with PRRT2 mutations in the univariate analysis. Multivariate logistic regression analysis demonstrated that age of onset [odds ratio (OR) = 0.59, P = 0.025] and premonitory sensation (OR = 10.67, P = 0.028) were independently associated with positive PRRT2 mutation.

Conclusions

PRRT2 mutations are common in patients with PKD, and a double PRRT2 mutation is reported for the first time. PRRT2 mutations are significantly associated with a younger age of onset and the presence of premonitory sensation in our population.

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