研究者詳細 - 石浦　浩之

論文 - 石浦　浩之

分割表示 225 件中 141 - 160 件目／全件表示 >>

Selective impairment of On-reading (Chinese-style pronunciation) in alexia with agraphia for kanji due to subcortical hemorrhage in the left posterior middle temporal gyrus 査読

Mizuho Yoshida, Toshihiro Hayashi, Kurumi Fujii, Hiroyuki Ishiura, Shoji Tsuji, Yasuhisa Sakurai

Neurocase 26 ( 4 ) 220 - 226 2020年7月

A novel mutation in the GBA2 gene in a Japanese patient with SPG46: A case report

Keiko Nakamura-Shindo, Kenjiro Ono, Kishin Koh, Hiroyuki Ishiura, Shoji Tsuji, Yoshihisa Takiyama, Masahito Yamada

eNeurologicalSci 19 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier B.V.

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder characterized by pyramidal weakness and spasticity of the lower limbs. SPG46, one of autosomal recessive HSP, is clinically characterized by spasticity and pyramidal weakness of the lower limbs, mental retardation, congenital bilateral cataract, thin corpus callosum, and hypogonadism in males. Mutations in the nonlysosomal glucosylceramidase β2 (GBA2) gene have been identified in patients with SPG46. A Japanese woman was identified with bilateral cataracts when she was in an elementary school. She felt falling easily, speaking unclearness, and difficulty in walking and raising her left leg in her 30s. Her neurological examination at the age of 44 revealed dysarthria, spasticity in the upper and lower extremities, increased jaw jerk and tendon reflexes in the extremities, bilateral extensor plantar reflexes, ataxia, and pollakiuria. Magnetic resonance imaging showed thinning of the corpus callosum body as well as atrophy in the pons and cerebellum. A novel homozygous c.1838A &gt
G (p.D613G) missense mutation was detected at exon 12 in GBA2. We diagnosed her illness as an autosomal-recessive form of hereditary SPG46. The clinical features matched previously reported phenotype of SPG46. This is the first report of a Japanese patient with SPG46 with a novel mutation in GBA2. We presume that the novel GBA2 missense mutation found in our patient would cause loss of GBA2 activity, resulting in the neurological manifestations of SPG46.

DOI： 10.1016/j.ensci.2020.100238

Clinical features of inherited neuropathy with BSCL2 mutations in Japan. 査読国際誌

Satoshi Ishihara, Yuji Okamoto, Hajime Tanabe, Akiko Yoshimura, Yujiro Higuchi, Jun-Hui Yuan, Akihiro Hashiguchi, Hiroyuki Ishiura, Jun Mitsui, Shugo Suwazono, Yasushi Oya, Masayuki Sasaki, Masanori Nakagawa, Shoji Tsuji, Yusuke Ohya, Hiroshi Takashima

Journal of the peripheral nervous system : JPNS 25 ( 2 ) 125 - 131 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene have been reported with different clinical phenotypes including Silver syndrome (SS)/spastic paraplegia 17 (SPG17), distal hereditary motor neuropathy type V (dHMN-V), and Charcot-Marie-Tooth (CMT) disease type 2. We screened 407 Japanese patients who were clinically suspected of having CMT by exome sequencing and searched mutations in BSCL2. As a result, we identified five patients with heterozygous mutations in BSCL2. We confirmed three cases of known mutations (p.N88S and p.S90L) and two cases of novel mutations (p.N88T and p.S141A). The clinical features of the cases with known mutations in Japan were similar to those previously reported in other countries. In particular, there were many cases with sensory disturbance. The case with p.N88T mutation showed severe phenotype such as early onset age and prominent vocal cord paresis. The case with p.S141A mutation showed characteristics of demyelinating neuropathy such as CMT disease type 1 by electrophysiological examination. In this article, we report the clinical features and spread of cases with BSCL2 mutation in a Japanese cohort.

DOI： 10.1111/jns.12369

Clinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy. 査読国際誌

Takashi Matsukawa, Tomotaka Yamamoto, Akira Honda, Takashi Toya, Hiroyuki Ishiura, Jun Mitsui, Masaki Tanaka, Akihito Hao, Akihito Shinohara, Mizuki Ogura, Keisuke Kataoka, Sachiko Seo, Keiki Kumano, Masataka Hosoi, Kensuke Narukawa, Megumi Yasunaga, Hiroaki Maki, Motoshi Ichikawa, Yasuhito Nannya, Yoichi Imai, Tsuyoshi Takahashi, Yuji Takahashi, Yuki Nagasako, Kyoko Yasaka, Kagari Koshi Mano, Miho Kawabe Matsukawa, Toji Miyagawa, Masashi Hamada, Kaori Sakuishi, Toshihiro Hayashi, Atsushi Iwata, Yasuo Terao, Jun Shimizu, Jun Goto, Harushi Mori, Akira Kunimatsu, Shigeki Aoki, Shin Hayashi, Fumihiko Nakamura, Syunya Arai, Kazunari Momma, Katsuhisa Ogata, Toshikazu Yoshida, Osamu Abe, Johji Inazawa, Tatsushi Toda, Mineo Kurokawa, Shoji Tsuji

Brain communications 2 ( 1 ) fcz048 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

Accumulated experience supports the efficacy of allogenic haematopoietic stem cell transplantation in arresting the progression of childhood-onset cerebral form of adrenoleukodystrophy in early stages. For adulthood-onset cerebral form of adrenoleukodystrophy, however, there have been only a few reports on haematopoietic stem cell transplantation and the clinical efficacy and safety of that for adulthood-onset cerebral form of adrenoleukodystrophy remain to be established. To evaluate the clinical efficacy and safety of haematopoietic stem cell transplantation, we conducted haematopoietic stem cell transplantation on 12 patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy in a single-institution-based prospective study. Through careful prospective follow-up of 45 male adrenoleukodystrophy patients, we aimed to enrol patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy at early stages. Indications for haematopoietic stem cell transplantation included cerebral form of adrenoleukodystrophy or cerebello-brainstem form of adrenoleukodystrophy with Loes scores up to 13, the presence of progressively enlarging white matter lesions and/or lesions with gadolinium enhancement on brain MRI. Clinical outcomes of haematopoietic stem cell transplantation were evaluated by the survival rate as well as by serial evaluation of clinical rating scale scores and neurological and MRI findings. Clinical courses of eight patients who did not undergo haematopoietic stem cell transplantation were also evaluated for comparison of the survival rate. All the patients who underwent haematopoietic stem cell transplantation survived to date with a median follow-up period of 28.6 months (4.2-125.3 months) without fatality. Neurological findings attributable to cerebral/cerebellar/brainstem lesions became stable or partially improved in all the patients. Gadolinium-enhanced brain lesions disappeared or became obscure within 3.5 months and the white matter lesions of MRI became stable or small. The median Loes scores before haematopoietic stem cell transplantation and at the last follow-up visit were 6.0 and 5.25, respectively. Of the eight patients who did not undergo haematopoietic stem cell transplantation, six patients died 69.1 months (median period; range 16.0-104.1 months) after the onset of the cerebral/cerebellar/brainstem lesions, confirming that the survival probability was significantly higher in patients with haematopoietic stem cell transplantation compared with that in patients without haematopoietic stem cell transplantation (P = 0.0089). The present study showed that haematopoietic stem cell transplantation was conducted safely and arrested the inflammatory demyelination in all the patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy when haematopoietic stem cell transplantation was conducted in the early stages. Further studies are warranted to optimize the procedures of haematopoietic stem cell transplantation for adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy.

DOI： 10.1093/braincomms/fcz048

VPS13D-related disorders presenting as a pure and complicated form of hereditary spastic paraplegia. 査読国際誌

Koh K, Ishiura H, Shimazaki H, Tsutsumiuchi M, Ichinose Y, Nan H, Hamada S, Ohtsuka T, Tsuji S, Takiyama Y

Molecular genetics & genomic medicine e1108 2019年12月

Spastic Paraplegia Accompanied by Extrapyramidal Sign and Frontal Cognitive Dysfunction. 査読

Ryo Sasaki, Yasuyuki Ohta, Kota Sato, Koh Tadokoro, Yoshiaki Takahashi, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Hiroyuki Ishiura, Shoji Tsuji, Koji Abe

Internal medicine (Tokyo, Japan) 58 ( 21 ) 3163 - 3165 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

A complicated form of spastic paraplegia is a neurodegenerative disorder presenting as progressive spasticity in the bilateral lower limbs accompanied by some clinical features. The present case showed spastic paralysis and hyperreflexia in all extremities as well as lead pipe rigidity in the neck and bilateral upper extremities (R < L), decreased scores on frontal cognitive tests, a decreased accumulation of the right dorsal putamen on a DAT scan, and hypoperfusion of the bilateral frontal lobes on 99mTc-ECD single photon emission computed tomography (SPECT). The present case provides a new spectrum of spastic paraplegia based on the evidence of clinical scores and the findings of brain functional imaging.

DOI： 10.2169/internalmedicine.2765-19

UBAP1 mutations cause juvenile-onset hereditary spastic paraplegias (SPG80) and impair UBAP1 targeting to endosomes. 査読国際誌

Haitian Nan, Yuta Ichinose, Masaki Tanaka, Kishin Koh, Hiroyuki Ishiura, Jun Mitsui, Heisuke Mizukami, Masafumi Morimoto, Shun Hamada, Toshihisa Ohtsuka, Shoji Tsuji, Yoshihisa Takiyama

Journal of human genetics 64 ( 11 ) 1055 - 1065 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

We aimed to find a new causative gene and elucidate the molecular mechanisms underlying a new type of hereditary spastic paraplegia (HSP). Patients with HSP were recruited from the Japan Spastic Paraplegia Research Consortium (JASPAC). Exome sequencing of genomic DNA from patients in four families was carried out, followed by Sanger sequencing of the UBAP1 gene. A mouse homolog of one UBAP1 frameshift mutation carried by one of the patients was created as a disease model. Functional properties of the UBAP1 wild type and UBAP1-mutant in mouse hippocampus neurons were examined. We identified three novel heterozygous loss of function mutations (c.425_426delAG, c.312delC, and c.535G>T) in the UBAP1 gene as the genetic cause of a new type of HSP (SPG80). All the patients presented identical clinical features of a pure type of juvenile-onset HSP. Functional studies on mouse hippocampal neurons revealed that the C-terminal deletion UBAP1-mutant of our disease model had lost its ability to bind ubiquitin in vitro. Overexpression of the UBAP1 wild type interacts directly with ubiquitin on enlarged endosomes, while the UBAP1-mutant cannot be recruited to endosome membranes. Our study demonstrated that mutations in the UBAP1 gene cause a new type of HSP and elucidated its pathogenesis. The full-length UBAP1 protein is involved in endosomal dynamics in neurons, while loss of UBAP1 function may perturb endosomal fusion and sorting of ubiquitinated cargos. These effects could be more prominent in neurons, thereby giving rise to the phenotype of a neurodegenerative disease such as HSP.

DOI： 10.1038/s10038-019-0670-9

Prominent Spasticity and Hyperreflexia of the Legs in a Nepalese Patient with Friedreich Ataxia. 査読

Hiroya Naruse, Yuji Takahashi, Hiroyuki Ishiura, Takashi Matsukawa, Jun Mitsui, Yaeko Ichikawa, Masashi Hamada, Jun Shimizu, Jun Goto, Tatsushi Toda, Shoji Tsuji

Internal medicine (Tokyo, Japan) 58 ( 19 ) 2865 - 2869 2019年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Friedreich ataxia (FRDA) is an autosomal recessive spinocerebellar ataxia caused by mutations of FXN. Hypotonus and hyporeflexia of the lower extremities are observed in most FRDA patients. Patients with hyperreflexia, called Friedreich ataxia with retained reflexes (FARR), have also been identified. We herein report the case of a 16-year-old Nepalese boy presenting with early-onset ataxia with prominent spasticity and hyperreflexia of the legs. Mutational analyses established the diagnosis of FRDA presenting as FARR. A haplotype analysis revealed that expanded alleles of the patient shared a common haplotype with Indian and European FRDA patients, suggesting that the mutation descended from a common founder.

DOI： 10.2169/internalmedicine.2953-19

Ataxic phenotype with altered CaV3.1 channel property in a mouse model for spinocerebellar ataxia 42. 査読国際誌

Shunta Hashiguchi, Hiroshi Doi, Misako Kunii, Yukihiro Nakamura, Misa Shimuta, Etsuko Suzuki, Shigeru Koyano, Masaki Okubo, Hitaru Kishida, Masaaki Shiina, Kazuhiro Ogata, Fumiko Hirashima, Yukichi Inoue, Shun Kubota, Noriko Hayashi, Haruko Nakamura, Keita Takahashi, Atsuko Katsumoto, Mikiko Tada, Kenichi Tanaka, Toshikuni Sasaoka, Satoko Miyatake, Noriko Miyake, Hirotomo Saitsu, Nozomu Sato, Kokoro Ozaki, Kiyobumi Ohta, Takanori Yokota, Hidehiro Mizusawa, Jun Mitsui, Hiroyuki Ishiura, Jun Yoshimura, Shinichi Morishita, Shoji Tsuji, Hideyuki Takeuchi, Kinya Ishikawa, Naomichi Matsumoto, Taro Ishikawa, Fumiaki Tanaka

Neurobiology of disease 130 104516 - 104516 2019年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Spinocerebellar ataxia 42 (SCA42) is a neurodegenerative disorder recently shown to be caused by c.5144G > A (p.Arg1715His) mutation in CACNA1G, which encodes the T-type voltage-gated calcium channel CaV3.1. Here, we describe a large Japanese family with SCA42. Postmortem pathological examination revealed severe cerebellar degeneration with prominent Purkinje cell loss without ubiquitin accumulation in an SCA42 patient. To determine whether this mutation causes ataxic symptoms and neurodegeneration, we generated knock-in mice harboring c.5168G > A (p.Arg1723His) mutation in Cacna1g, corresponding to the mutation identified in the SCA42 family. Both heterozygous and homozygous mutants developed an ataxic phenotype from the age of 11-20 weeks and showed Purkinje cell loss at 50 weeks old. Degenerative change of Purkinje cells and atrophic thinning of the molecular layer were conspicuous in homozygous knock-in mice. Electrophysiological analysis of Purkinje cells using acute cerebellar slices from young mice showed that the point mutation altered the voltage dependence of CaV3.1 channel activation and reduced the rebound action potentials after hyperpolarization, although it did not significantly affect the basic properties of synaptic transmission onto Purkinje cells. Finally, we revealed that the resonance of membrane potential of neurons in the inferior olivary nucleus was decreased in knock-in mice, which indicates that p.Arg1723His CaV3.1 mutation affects climbing fiber signaling to Purkinje cells. Altogether, our study shows not only that a point mutation in CACNA1G causes an ataxic phenotype and Purkinje cell degeneration in a mouse model, but also that the electrophysiological abnormalities at an early stage of SCA42 precede Purkinje cell loss.

DOI： 10.1016/j.nbd.2019.104516

Sporadic progressive myoclonic epilepsy with early‐onset dementia caused by a de novo mutation in PSEN1

Tomoya Taminato, Manabu Araki, Noriko Sato, Hiroyuki Ishiura, Jun Mitsui, Jun Yoshimura, Koichiro Doi, Shinichi Morishita, Shoji Tsuji, Yuji Takahashi

Neurology and Clinical Neuroscience 7 ( 5 ) 294 - 296 2019年9月

Functional evaluation of PDGFB-variants in idiopathic basal ganglia calcification, using patient-derived iPS cells. 査読国際誌

Shin-Ichiro Sekine, Masayuki Kaneko, Masaki Tanaka, Yuhei Ninomiya, Hisaka Kurita, Masatoshi Inden, Megumi Yamada, Yuichi Hayashi, Takashi Inuzuka, Jun Mitsui, Hiroyuki Ishiura, Atsushi Iwata, Hiroto Fujigasaki, Hisamitsu Tamaki, Ryusei Tamaki, Shinsuke Kito, Yoshiharu Taguchi, Kortaro Tanaka, Naoki Atsuta, Gen Sobue, Takayuki Kondo, Haruhisa Inoue, Shoji Tsuji, Isao Hozumi

Scientific reports 9 ( 1 ) 5698 - 5698 2019年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Causative genes in patients with idiopathic basal ganglia calcification (IBGC) (also called primary familial brain calcification (PFBC)) have been reported in the past several years. In this study, we surveyed the clinical and neuroimaging data of 70 sporadic patients and 16 families (86 unrelated probands in total) in Japan, and studied variants of PDGFB gene in the patients. Variant analyses of PDGFB showed four novel pathogenic variants, namely, two splice site variants (c.160 + 2T > A and c.457-1G > T), one deletion variant (c.33_34delCT), and one insertion variant (c.342_343insG). Moreover, we developed iPS cells (iPSCs) from three patients with PDGFB variants (c.160 + 2T > A, c.457-1G > T, and c.33_34 delCT) and induced endothelial cells. Enzyme-linked immunoassay analysis showed that the levels of PDGF-BB, a homodimer of PDGF-B, in the blood sera of patients with PDGFB variants were significantly decreased to 34.0% of that of the control levels. Those in the culture media of the endothelial cells derived from iPSCs of patients also significantly decreased to 58.6% of the control levels. As the endothelial cells developed from iPSCs of the patients showed a phenotype of the disease, further studies using IBGC-specific iPSCs will give us more information on the pathophysiology and the therapy of IBGC in the future.

DOI： 10.1038/s41598-019-42115-y

The novel de novo mutation of KIF1A gene as the cause for Spastic paraplegia 30 in a Japanese case. 査読国際誌

Yoshikawa K, Kuwahara M, Saigoh K, Ishiura H, Yamagishi Y, Hamano Y, Samukawa M, Suzuki H, Hirano M, Mitsui Y, Tsuji S, Kusunoki S

eNeurologicalSci 14 34 - 37 2019年3月

A novel homozygous mutation of the TFG gene in a patient with early onset spastic paraplegia and later onset sensorimotor polyneuropathy. 査読国際誌

Takuya Miyabayashi, Tatsuhiro Ochiai, Naoki Suzuki, Masashi Aoki, Takehiko Inui, Yukimune Okubo, Ryo Sato, Noriko Togashi, Hiroshi Takashima, Hiroyuki Ishiura, Shoji Tsuji, Kishin Koh, Yoshihisa Takiyama, Kazuhiro Haginoya

Journal of human genetics 64 ( 2 ) 171 - 176 2019年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

The tropomyosin-receptor kinase fused gene (TFG) has recently been implicated in several distinct hereditary disorders, including the autosomal-recessive form of complicated hereditary spastic paraplegia called SPG57. Previously, three homozygous variants of the TFG gene were reported in five families with SPG57, in which early onset spastic paraplegia, optic atrophy, and peripheral neuropathy were variably identified. Here, we present the first Japanese patient with SPG57, and have added a homozygous p.Ile66Thr variant as the fourth SPG57 genotype.

DOI： 10.1038/s10038-018-0538-4

Correction: PLA2G6-associated neurodegeneration presenting as a complicated form of hereditary spastic paraplegia. 査読国際誌

Kishin Koh, Yuta Ichinose, Hiroyuki Ishiura, Haitian Nan, Jun Mitsui, Junya Takahashi, Wakiro Sato, Yoshiaki Itoh, Kyoko Hoshino, Shoji Tsuji, Yoshihisa Takiyama

Journal of human genetics 64 ( 1 ) 61 - 63 2019年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

The originally published version of this article contained an error in Fig. 1 and Table 2. The correct figure and table of this article should have read as below. This has now been corrected in the PDF and HTML versions of the article. The authors apologize for any inconvenience caused.

DOI： 10.1038/s10038-018-0533-9

PLA2G6-associated neurodegeneration presenting as a complicated form of hereditary spastic paraplegia. 査読国際誌

Kishin Koh, Yuta Ichinose, Hiroyuki Ishiura, Haitian Nan, Jun Mitsui, Junya Takahashi, Wakiro Sato, Yoshiaki Itoh, Kyoko Hoshino, Shoji Tsuji, Yoshihisa Takiyama

Journal of human genetics 64 ( 1 ) 55 - 59 2019年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

PLA2G6-associated neurodegeneration (PLAN) comprises heterogeneous neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation 2B, and Parkinson disease 14 (PARK14). In addition, very recently, PLA2G6 mutations have been reported to represent a phenotype of hereditary spastic paraplegia (HSP). In this study, we screened 383 HSP families to clarify the frequency of PLA2G6 mutations in the Japan Spastic Paraplegia Research Consortium, and revealed the clinical characteristics of HSP with PLA2G6 mutations. We found three families with compound heterozygous mutations of the PLA2G6 gene, c.517 C > T/c.1634A > G, c.662 T > C/c.991 G > T, and c.1187-2 A > G/c.1933C > T, and one family with a homozygous mutation of the PLA2G6 gene, c.1904G > A/c.1904G > A. All three families with compound heterozygous mutations presented a uniform phenotype of a complicated form of HSP with infantile/child-onset spastic paraplegia, cerebellar ataxia, and mental retardation. On the other hand, the family with a homozygous mutation presented a late-onset complicated form of HSP with parkinsonism. This study may extend the clinical and genetic findings for PLAN.

DOI： 10.1038/s10038-018-0519-7

Atypical Familial Amyotrophic Lateral Sclerosis with Slowly Progressing Lower Extremities-predominant Late-onset Muscular Weakness and Atrophy. 査読

Jumpei Togawa, Takekazu Ohi, Jun-Hui Yuan, Hiroshi Takashima, Hirokazu Furuya, Shinji Takechi, Junko Fujitake, Saki Hayashi, Hiroyuki Ishiura, Hiroya Naruse, Jun Mitsui, Shoji Tsuji

Internal medicine (Tokyo, Japan) 58 ( 13 ) 1851 - 1858 2019年

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by the progressive loss of the upper and lower motor neurons that progresses to paralysis of almost all skeletal muscles of the extremities, bulbar, and respiratory system. Although most ALS cases are sporadic, about 10% are dominantly inherited. We herein report an atypical phenotype of familial ALS (fALS). To elucidate the phenotype-genotype correlation of this atypical phenotype of fALS, clinical and genetic investigations were performed. Methods and Patients Five sibling patients (three men, two women) from a Japanese family and one healthy sibling (a woman) were clinically interviewed and examined. Genetic analyses, including genome-wide linkage analyses and whole-exome sequencing, were performed using genomic DNA extracted from the peripheral blood samples of these siblings. Results The clinical features of fALS are characterized by slow progression (mean duration of the disease±standard deviation [SD]: 19.6±3.9 years) and lower extremities-predominant late-onset muscular weakness (mean onset of muscular weakness±SD: 52.8±2.6 years). Genetic analyses revealed novel heterozygous missense mutations of c.2668C>T, p.R890C in the PLEC gene and c.421G>C, p.V141L in the ST3GAL6 gene in all affected siblings. Conclusion A new atypical fALS family with a benign clinical course is herein reported. We identified two candidate gene mutations of PLEC and ST3GAL6 linked to this phenotype.

DOI： 10.2169/internalmedicine.2222-18

An Autopsy Case of Familial Neuronal Intranuclear Inclusion Disease with Dementia and Neuropathy. 査読

Nanaka Yamaguchi, Tatsuo Mano, Ryo Ohtomo, Hiroyuki Ishiura, M Asem Almansour, Harushi Mori, Junko Kanda, Yuichiro Shirota, Kenichiro Taira, Teppei Morikawa, Masako Ikemura, Yasuo Yanagi, Shigeo Murayama, Jun Shimizu, Yasuhisa Sakurai, Shoji Tsuji, Atsushi Iwata

Internal medicine (Tokyo, Japan) 57 ( 23 ) 3459 - 3462 2018年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with marked variety in its clinical manifestations. While characteristic neuroimaging and skin biopsy findings are important clues to the diagnosis, autopsy studies are still important for confirming the exact disease features. We herein report the case of a patient who received an antemortem diagnosis of familial NIID with dementia-dominant phenotype that was later confirmed by an autopsy. Our report is the first to document a case of autopsy-confirmed NIID involving both cognitive impairment and sensorimotor neuropathy.

DOI： 10.2169/internalmedicine.1141-18

成人発症型ALDに対するHSCT 脳障害の早期診断をもたらす背景因子(HSCT for adult-onset ALD: Background factors leading to early diagnosis of the brain involvement)

Matsukawa Takashi, Mitsui Jun, Ishiura Hiroyuki, Yamamoto Tomotaka, Hao Akihito, Matsukawa Miho, Tanaka Masaki, Chang Hyangri, Miyagawa Toji, Hamada Masashi, Takahashi Yuji, Hayashi Toshihiro, Iwata Atsushi, Shimizu Jun, Goto Jun, Toda Tatsushi, Tsuji Shoji

臨床神経学 58 ( Suppl. ) S371 - S371 2018年12月

The pathogenesis linked to coenzyme Q10 insufficiency in iPSC-derived neurons from patients with multiple-system atrophy. 査読国際誌

Fumiko Kusunoki Nakamoto, Satoshi Okamoto, Jun Mitsui, Takefumi Sone, Mitsuru Ishikawa, Yorihiro Yamamoto, Yumi Kanegae, Yuhki Nakatake, Kent Imaizumi, Hiroyuki Ishiura, Shoji Tsuji, Hideyuki Okano

Scientific reports 8 ( 1 ) 14215 - 14215 2018年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Multiple-system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure with various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. We previously reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of coenzyme Q10, are associated with MSA. Here, we report functional deficiencies in mitochondrial respiration and the antioxidative system in induced pluripotent stem cell (iPSC)-derived neurons from an MSA patient with compound heterozygous COQ2 mutations. The functional deficiencies were rescued by site-specific CRISPR/Cas9-mediated gene corrections. We also report an increase in apoptosis of iPSC-derived neurons from MSA patients. Coenzyme Q10 reduced apoptosis of neurons from the MSA patient with compound heterozygous COQ2 mutations. Our results reveal that cellular dysfunctions attributable to decreased coenzyme Q10 levels are related to neuronal death in MSA, particularly in patients with COQ2 variants, and may contribute to the development of therapy using coenzyme Q10 supplementation.

DOI： 10.1038/s41598-018-32573-1

Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment. 査読国際誌

Kishin Koh, Hiroyuki Ishiura, Minako Beppu, Haruo Shimazaki, Yuta Ichinose, Jun Mitsui, Satoshi Kuwabara, Shoji Tsuji, Yoshihisa Takiyama

Journal of human genetics 63 ( 9 ) 1009 - 1013 2018年9月

記述言語：英語

Hereditary spastic paraplegias (HSPs) are characterized by various inherited disorders in which weakness and spasticity of the lower extremities are the predominant symptoms. Recently, HSP caused by ALDH18A1 mutations has been reported as SPG9 with autosomal dominant (SPG9A) and autosomal recessive (SPG9B) transmission. In this study, we obtained clinical and genetic findings in two Japanese families with SPG9B. One family had a novel compound heterozygous mutation (c.1321 C > T/c.1994G > A) in the ALDH18A1 gene. The other family had a homozygous mutation (c.383 G > A/c.383 G > A) in the ALDH18A1 gene. To date, only two SPG9B families with ALDH18A1 mutations have been reported. This is the first report of SPG9 in non-Caucasians. Furthermore, we found cerebellar ataxia in one family, although cerebellar ataxia has not been reported in SPG9B so far. SPG9B might involve a complicated HSP including cerebellar ataxia and cognitive impairment. This study expands the clinical and genetic spectrum of ALDH18A1-related disorders.

DOI： 10.1038/s10038-018-0477-0

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