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Identification of a new family of spinocerebellar ataxia type 14 in the japanese spinocerebellar ataxia population by the screening of PRKCG exon 4

Authors

  • Keiko Hiramoto MD, PhD,

    1. Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
    2. Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
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  • Hideshi Kawakami MD, PhD,

    Corresponding author
    1. Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
    • Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
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  • Kimiko Inoue MD,

    1. Department of Neurology, Hyogo Rehabilitation Center Hospital, Nishi-ku, Kobe, Japan
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  • Takahiro Seki PhD,

    1. Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
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  • Hirofumi Maruyama MD, PhD,

    1. Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
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  • Hiroyuki Morino MD, PhD,

    1. Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
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  • Masayasu Matsumoto MD, PhD,

    1. Department of Clinical Neuroscience and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
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  • Kaoru Kurisu MD, PhD,

    1. Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
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  • Norio Sakai MD, PhD

    1. Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
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Abstract

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia and intermittent axial myoclonus. Various mutations have been found in the PRKCG gene encoding protein kinase C γ in SCA14 families. Most of those mutations have been found in exon 4 of the PRKCG gene. We performed polymerase chain reaction (PCR)–based screening to clarify the approximate morbidity rate of the disease in the Japanese SCA population. We screened exon 4 of the PRKCG gene in 882 SCA patients with undefined etiologies using denaturing high-performance liquid chromatography and subsequent direct sequencing. We found a novel C/T missense mutation with a Ser119-to-Phe substitution (S119F) in 2 patients and subsequently found that they belonged to the same family. This S119F mutation was not found in 259 control individuals. Further PCR-based analysis revealed an additional 5 members with the same mutation in this family. Cerebellar ataxia was manifested in 5 of those 7 members. The main symptom in 4 of the 5 affected members was pure cerebellar ataxia with late onset. They had no myoclonus, extrapyramidal signs, ophthalmoplegia, or intellectual disturbance, some of which were found in previously reported SCA families. One patient showed intractable epilepsy, severe walking disturbance, and trunk ataxia with early onset. The results of this study suggest that the frequency of SCA14 in the Japanese SCA population is very low. © 2006 Movement Disorder Society

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