基本情報
- 所属
- 自治医科大学 医学部 小児科学講座 発達医学部門 教授
- 学位
- 博士(医学)(2008年3月)
- ORCID ID
- https://orcid.org/0000-0001-9256-5591
- J-GLOBAL ID
- 201101004536757106
- researchmap会員ID
- B000003156
- 外部リンク
主要な経歴
13-
2023年4月 - 現在
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2019年4月 - 現在
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2017年4月 - 2023年3月
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2016年4月 - 2017年3月
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2005年4月 - 2008年3月
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1998年5月 - 2003年4月
委員歴
9-
2021年6月 - 現在
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2021年6月 - 現在
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2018年10月 - 現在
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2017年11月 - 現在
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2016年 - 現在
受賞
5論文
131-
Scientific Reports 9(1) 2019年11月8日 査読有り筆頭著者<title>Abstract</title> Idiopathic restless legs syndrome (RLS) has a genetic basis wherein <italic>BTBD9</italic> is associated with a higher risk of RLS. Hemodialysis patients also exhibit higher rates of RLS compared with the healthy population. However, little is known about the relationship of <italic>BTBD9</italic> and end-stage renal disease to RLS pathophysiology. Here we evaluated sleep and leg muscle activity of <italic>Btbd9</italic> mutant (MT) mice after administration of serum from patients with either idiopathic or RLS due to end-stage renal disease (renal RLS) and investigated the efficacy of treatment with the dopamine agonist rotigotine. At baseline, the amount of rapid eye movement (REM) sleep was decreased and leg muscle activity during non-REM (NREM) sleep was increased in MT mice compared to wild-type (WT) mice. Wake-promoting effects of rotigotine were attenuated by injection of serum from RLS patients in both WT and MT mice. Leg muscle activity during NREM sleep was increased only in MT mice injected with serum from RLS patients of ideiopatic and renal RLS. Subsequent treatment with rotigotine ameliorated this altered leg muscle activity. Together these results support previous reports showing a relationship between the Btbd9/dopamine system and RLS, and elucidate in part the pathophysiology of RLS.
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Brain and Development 41(8) 726-730 2019年9月 査読有りINTRODUCTION: Neuronal ceroid lipofuscinoses (NCLs; CLN) are mainly autosomal recessive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigments in neuronal and other cells. Symptoms include visual disabilities, motor decline, and epilepsy. Causative genes are CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8, CLN10, CLN11, CLN12, CLN13, and CLN14. We present the fourth Japanese case with a CLN6 mutation. CASE PRESENTATION: At 3 years of age, our patient became clumsy and fell down easily. He developed focal seizures with impaired consciousness and was started on carbamazepine. He showed ataxic walking and dysarthria with increased deep tendon reflexes. Interictal electroencephalogram revealed slow waves in the left temporal and occipital areas. Brain magnetic resonance imaging showed cerebellar atrophy and ventriculomegaly. In optical coherence tomography (OCT), the inner layer of the retina was thick and highly reflective. Exome sequencing revealed a known homozygous mutation, C.794_976del, p. (Ser265del) in CLN6. DISCUSSION: A total of 130 cases of NCL with CLN6 mutations have been reported globally, of which only four were from Japan including the current patient. The deletion of serine at position 265 has been reported in six cases. Ser265 is located in a region of short repeated sequences that is susceptible to mutation. Clinical trials of gene therapy using adeno-associated virus serotype 9 have started for NCL6, making early diagnosis crucial. OCT examination might be helpful in achieving a diagnosis.
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IEEE Transactions on Magnetics 2019年6月
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Brain and Development 41(5) 465-469 2019年5月 査読有り
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IEEE Transactions on Applied Superconductivity 2019年3月
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IEEE Transactions on Applied Superconductivity 2019年3月
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IEEE Transactions on Magnetics 2018年11月
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IEEE Transactions on Magnetics 2018年11月
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IEEE Transactions on Magnetics 2018年11月
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日本小児科学会雑誌 122(6) 1109-1109 2018年6月 査読有り
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IEEE Transactions on Magnetics 2018年3月
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Clinical Genetics 93(5) 1103-1106 2018年 査読有り© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1-year-old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue-native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3.
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Pediatrics International 59(8) 951-954 2017年 査読有り責任著者Herein we report the case of a 6-year-old girl with autism spectrum disorder (ASD) and weakness in the distal portion of the right upper limb. Although difficult to perform, nerve conduction studies indicated demyelinating neuropathy. Magnetic resonance imaging (MRI) showed swelling a nd high-intensity signals in the right brachial plexus and cervical spinal roots. The symptoms recovered after a single course of i.v. immunoglobulin. Electrophysiological indices and MRI findings also improved after treatment. This case demonstrates the utility of neuroimaging in addition to electrophysiological assessments for the diagnosis of demyelinating neuropathy, particularly in young patients with ASD.
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Brain and Development 2017年 査読有り責任著者
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Nature Genetics. 49(3) 457-464 2017年 査読有り
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Brain and Development 39(3) 231-235 2017年 査読有り筆頭著者責任著者Introduction: Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID). Methods: We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment >= 2 years, (2) younger than 20 years old, and (3) received oral levetiracetam treatment for >= 6 months. We assessed the relationships of these outcomes with MRI findings and ID status. Results: Eighteen (37%) patients achieved a >= 50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patientg who achieved a 3 >= 50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively. Conclusions: Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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Clinical Genetics 90(6) 526-535 2016年 査読有りJoubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the molar tooth sign'. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole-exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24+6) families (83.3%). We identified eight mutated genes in 27 (21+6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012-12T>A (75.0%), an allele that has not been reported in non-Japanese populations. Therefore c.6012-12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet-Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.
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No To Hattatsu 48(3) 177-183 2016年 査読有り筆頭著者責任著者
MISC
62書籍等出版物
6-
診断と治療社 2020年 (ISBN: 9784787823823)
担当経験のある科目(授業)
5-
小児実践看護学 (自治医科大学)
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小児看護専門看護実習 (自治医科大学大学院修士課程)
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小児科総括講義 (自治医科大学)
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成長発達講義 (自治医科大学)
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成育医学講義 (自治医科大学大学院博士課程)
所属学協会
3-
2023年6月 - 現在
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2022年6月 - 現在
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- 現在
主要な共同研究・競争的資金等の研究課題
16-
厚生労働省 難治性疾患政策研究事業 2024年4月 - 2027年3月
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日本医療研究開発機構 難治性疾患実用化研究事業 2024年4月 - 2027年3月
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日本医療研究開発機構 再生医療等実用化研究事業 2024年4月 - 2027年3月
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AMED 再生・細胞医療・遺伝子治療実現加速化プログラム 2023年7月 - 2025年3月
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難治性疾患実用化研究事業 治験準備 (ステップ1) 2021年4月 - 2024年3月
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難治性疾患実用化研究事業 薬事承認を目指すシーズ探索研究 (ステップ0) 2021年4月 - 2024年3月
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厚生労働省 2023年4月