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Familial paroxysmal kinesigenic dyskinesia with a novel missense variant (Arg2866Trp) in NBEA

Journal of Human Genetics volume 66, pages 805–811 (2021)Cite this article

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Abstract

Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by episodic involuntary movement attacks triggered by sudden movements, acceleration, or intention to move. We ascertained two Japanese familial cases with PKD. The proband is a 22-year-old woman who had noted sudden brief (<30 s) of involuntary movements provoked by kinesigenic trigger such as starting to run, getting on a train, picking up a telephone receiver and so on at the age of 14. Interictal brain single photon emission computed tomography (SPECT) showed hyperperfusion in the left thalamus. A 46-year-old woman, the mother of the proband was also suffering from brief attacks triggered by starting to run in her high school days. On neurological examination, both showed no abnormality. Whole exome sequencing combined with rigorous filtering revealed two heterozygous nonsynonymous variants (NM_001447: c.8976G > C [p.Gln2992His] in FAT2 and NM_015678: c.8596C > T [p.Arg2866Trp] in NBEA). Real time quantitative PCR analysis of Nbea mRNA levels in the developing rat brain revealed peak at postnatal day 28 and decline at postnatal day 56. This result might match the most common clinical course of PKD from the point of view of the most common age at remission. NBEA has been reported to be responsible for neurodevelopmental disease accompanied by epilepsy. We concluded the variant in NBEA most likely to be responsible for our familial cases of PKD.

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Data availability

The NBEA variant data have been deposited to and openly available from ClinVar (Submission IDs: SUB7619122, https://www.ncbi.nlm.nih.gov/clinvar/variation/973380/). The FAT2 variant data have been deposited to and openly available from ClinVar (Submission IDs: SUB8292369, https://www.ncbi.nlm.nih.gov/clinvar/variation/992659/). The NUP98 variant data have been deposited to and openly available from ClinVar (Submission IDs: SUB8311015 https://www.ncbi.nlm.nih.gov/clinvar/variation/992658/). The data sets of this study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University.

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Authors and Affiliations

  1. Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, 791-0295, Japan

    Shiroh Miura

  2. Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan

    Shiroh Miura, Tomofumi Shimojo, Takuya Morikawa & Hiroki Shibata

  3. Department of Neurology, Fukuoka Sanno Hospital, Fukuoka, 814-0001, Japan

    Takashi Kamada

  4. Department of Radiology, Kurume University School of Medicine, Kurume, 830-0011, Japan

    Yusuke Uchiyama & Seiji Kurata

  5. Department of Food and Nutrition, Beppu University Junior College, Beppu, 874-8501, Japan

    Ryuta Fujioka

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Correspondence to Hiroki Shibata.

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Miura, S., Shimojo, T., Morikawa, T. et al. Familial paroxysmal kinesigenic dyskinesia with a novel missense variant (Arg2866Trp) in NBEA. J Hum Genet 66, 805–811 (2021). https://doi.org/10.1038/s10038-021-00914-0

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