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Novel pathogenic VPS13A gene mutations in Japanese patients with chorea-acanthocytosis
Yoshiaki Nishida1, Masayuki Nakamura1, Yuka Urata1
1Kagoshima University Graduate School of Medical and Dental Sciences (Y.N., M.N., Y.U., K. Kasamo, H.H., I.Y., A.S.), Department of Psychiatry, Kagoshima, Japan; Epilepsy Center (M.M.), Department of Neurology, Nakamura Memorial Hospital, Hokkaido, Japan; Department of Psychiatry and Neurology (K. Sakurai.), Hokkaido University Graduate School of Medicine, Hokkaido, Japan; Department of Neurology (Y.O., Y.M.), Kochi Medical School, Kochi, Japan; Shinjyuku Neuro Clinic (M.W.), Tokyo, Japan; Department of Neurology (K. Yoshida and K. Yamane), Neurological Institute, Ohta-Atami Hospital, Fukushima, Japan; Department of Neurology (N.M., R.O.), Tokyo Metropolitan Neurological Hospital, Tokyo, Japan; Division of Neurology (T.U., H.T.), Kobe University Graduate School of Medicine, Hyogo, Japan; Department of Neurology (N.W., Y.S., T.S., Y.T., M.A.), National Center of Neurology and Psychiatry Hospital, Tokyo, Japan; Department of Neurology (K. Shibano), Akita Red Cross Hospital, Japan; Amagasaki General Medical Center (A.H.), Hyogo, Japan; Department of Neurology (K.M., K.O.), National Hospital Organization Higashisaitama National Hospital, Saitama, Japan; Department of Neurology (K. Kakuda, H.M.), Graduate School of Medicine, Osaka University, Japan; Ikebe Clinic (T.A.), Shizuoka, Japan; Department of Psychiatry (T.F.), National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Neurology (K.T., H.S.-T.), Tenri Hospital, Nara, Japan; and Department of Neurology (K.T., H.S.-T.), Graduate School of Medicine, Kyoto University, Japan.
Objective:
To identify mutations in vacuolar protein sorting 13A (VPS13A) for Japanese patients with suspected chorea-acanthocytosis (ChAc).
Methods:
We performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis of the VPS13A gene, and chorein Western blotting of erythrocyte ghosts. As the results of the analysis, 17 patients were molecularly diagnosed with ChAc. In addition, we investigated the distribution of VPS13A gene mutations and clinical symptoms in a total of 39 molecularly diagnosed Japanese patients with ChAc, including 22 previously reported cases.
Results:
We identified 11 novel pathogenic mutations, including 1 novel CNV. Excluding 5 patients with the unknown symptoms, 97.1% of patients displayed various neuropsychiatric symptoms or forms of cognitive dysfunction during the course of disease. The patients carrying the 2 major mutations representing over half of the mutations, exon 60-61 deletion and exon 37 c.4411C>T (R1471X), were localized in western Japan.
Conclusions:
We identified 13 different mutations in VPS13A, including 11 novel mutations, and verified the clinical manifestations in 39 Japanese patients with ChAc.
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