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Dive into the research topics where Naoya Morisada is active.

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Featured researches published by Naoya Morisada.


Neurology | 2014

Genotype–phenotype correlations in alternating hemiplegia of childhood

Masayuki Sasaki; Atsushi Ishii; Yoshiaki Saito; Naoya Morisada; Kazumoto Iijima; Satoshi Takada; Atsushi Araki; Yuko Tanabe; Hidee Arai; Sumimasa Yamashita; Tsukasa Ohashi; Yoichiro Oda; Hiroshi Ichiseki; Shininchi Hirabayashi; Akihiro Yasuhara; Hisashi Kawawaki; Sadami Kimura; Masayuki Shimono; Seiro Narumiya; Motomasa Suzuki; Takeshi Yoshida; Yoshinobu Oyazato; Shuichi Tsuneishi; Shiro Ozasa; Kenji Yokochi; Sunao Dejima; Tomoyuki Akiyama; Nobuyuki Kishi; Ryutaro Kira; Toshio Ikeda

Objective: Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype–phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC. Methods: Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care. Results: Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3: Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations. Conclusions: The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.


Kidney International | 2014

Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IV α5 chain

Yuya Hashimura; Kandai Nozu; Hiroshi Kaito; Koichi Nakanishi; Xue Jun Fu; Hiromi Ohtsubo; Fusako Hashimoto; Masafumi Oka; Takeshi Ninchoji; Shingo Ishimori; Naoya Morisada; Natsuki Matsunoshita; Naohiro Kamiyoshi; Norishige Yoshikawa; Kazumoto Iijima

X-linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain (α5(IV)). Complete absence of α5(IV) in the renal basal membrane is considered a pathological characteristic in male patients; however, positive α5(IV) staining has been found in over 20% of patients. We retrospectively studied 52 genetically diagnosed male X-linked Alport syndrome patients to evaluate differences in clinical characteristics and renal outcomes between 15 α5(IV)-positive and 37 α5(IV)-negative patients. Thirteen patients in the α5(IV)-positive group had non-truncating mutations consisting of nine missense mutations, three in-frame deletions, and one splice-site mutation resulting in small in-frame deletions of transcripts. The remaining two showed somatic mutations with mosaicism. Missense mutations in the α5(IV)-positive group were more likely to be located before exon 25 compared with missense mutations in the α5(IV)-negative group. Furthermore, urinary protein levels were significantly lower and the age at onset of end-stage renal disease was significantly higher in the positive group than in the negative group. These results help to clarify the milder clinical manifestations and molecular characteristics of male X-linked Alport syndrome patients expressing the α5(IV) chain.


Cardiovascular Research | 2010

Severe dyslipidaemia, atherosclerosis, and sudden cardiac death in mice lacking all NO synthases fed a high-fat diet

Yasuko Yatera; Kiyoko Shibata; Yumi Furuno; Ken Sabanai; Naoya Morisada; Sei Nakata; Tsuyoshi Morishita; Yumiko Toyohira; Ke-Yong Wang; Akihide Tanimoto; Yasuyuki Sasaguri; Hiromi Tasaki; Yasuhide Nakashima; Hiroaki Shimokawa; Nobuyuki Yanagihara; Yutaka Otsuji; Masato Tsutsui

AIMS The precise role of the nitric oxide synthase (NOS) system in lipid metabolism remains to be elucidated. We addressed this point in mice that we have recently developed and that lack all three NOS isoforms. METHODS AND RESULTS Wild-type (WT), singly, doubly, and triply NOS(-/-) mice were fed either a regular or high-cholesterol diet for 3-5 months. The high-cholesterol diet significantly increased serum low-density lipoprotein (LDL) cholesterol levels in all the genotypes when compared with the regular diet. Importantly, when compared with the WT genotype, the serum LDL cholesterol levels in the high-cholesterol diet were significantly and markedly elevated only in the triply NOS(-/-) genotype, but not in any singly or doubly NOS(-/-) genotypes, and this was associated with remarkable atherosclerosis and sudden cardiac death, which occurred mainly in the 4-5 months after the high-cholesterol diet. Finally, hepatic LDL receptor expression was markedly reduced only in the triply NOS(-/-) genotype, accounting for the diet-induced dyslipidaemia in the genotype. CONCLUSION These results provide the first direct evidence that complete disruption of all NOS genes causes severe dyslipidaemia, atherosclerosis, and sudden cardiac death in response to a high-fat diet in mice in vivo through the down-regulation of the hepatic LDL receptor, demonstrating the critical role of the whole endogenous NOS system in maintaining lipid homeostasis.


Genetics in Medicine | 2016

Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo–Bartter/Gitelman syndrome based on clinical characteristics

Natsuki Matsunoshita; Kandai Nozu; Akemi Shono; Yoshimi Nozu; Xue Jun Fu; Naoya Morisada; Naohiro Kamiyoshi; Hiromi Ohtsubo; Takeshi Ninchoji; Shogo Minamikawa; Tomohiko Yamamura; Koichi Nakanishi; Norishige Yoshikawa; Yuko Shima; Hiroshi Kaito; Kazumoto Iijima

Purpose:Phenotypic overlap exists among type III Bartter syndrome (BS), Gitelman syndrome (GS), and pseudo-BS/GS (p-BS/GS), which are clinically difficult to distinguish. We aimed to clarify the differences between these diseases, allowing accurate diagnosis based on their clinical features.Methods:A total of 163 patients with genetically defined type III BS (n = 30), GS (n = 90), and p-BS/GS (n = 43) were included. Age at diagnosis, sex, body mass index, estimated glomerular filtration rate, and serum and urine electrolyte concentrations were determined.Results:Patients with p-BS/GS were significantly older at diagnosis than those with type III BS and GS. Patients with p-BS/GS included a significantly higher percentage of women and had a lower body mass index and estimated glomerular filtration rate than did patients with GS. Although hypomagnesemia and hypocalciuria were predominant biochemical findings in patients with GS, 17 and 23% of patients with type III BS and p-BS/GS, respectively, also showed these abnormalities. Of patients with type III BS, GS, and p-BS/GS, 40, 12, and 63%, respectively, presented with chronic kidney disease.Conclusions:This study clarified the clinical differences between BS, GS, and p-BS/GS for the first time, which will help clinicians establish differential diagnoses for these three conditions.Genet Med 18 2, 180–188.


Clinical Journal of The American Society of Nephrology | 2016

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome

Naohiro Kamiyoshi; Kandai Nozu; Xue Jun Fu; Naoya Morisada; Yoshimi Nozu; Ming Juan Ye; Aya Imafuku; Kenichiro Miura; Tomohiko Yamamura; Shogo Minamikawa; Akemi Shono; Takeshi Ninchoji; Ichiro Morioka; Koichi Nakanishi; Norishige Yoshikawa; Hiroshi Kaito; Kazumoto Iijima

BACKGROUND AND OBJECTIVES Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport-related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. RESULTS The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte-related genes. CONCLUSIONS The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X-linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte-related genes.


Pediatrics International | 2014

Branchio-oto-renal syndrome: Comprehensive review based on nationwide surveillance in Japan

Naoya Morisada; Kandai Nozu; Kazumoto Iijima

Branchio‐oto‐renal (BOR) syndrome is an autosomal dominant disorder characterized by branchiogenic malformation, hearing loss and renal anomalies. The prevalence of BOR syndrome is 1/40 000 in Western countries, and nationwide surveillance in 2009–2010 identified approximately 250 BOR patients in Japan. Three causative genes for BOR syndrome have been reported thus far: EYA1, SIX1, and SIX5, but the causative genes for approximately half of all BOR patients remain unknown. This review article discusses the epidemiology, clinical symptoms, genetic background and management of BOR syndrome.


Early Human Development | 2013

Metabolomics analysis of umbilical cord blood clarifies changes in saccharides associated with delivery method

Fusako Hashimoto; Shin Nishiumi; Osamu Miyake; Hitomi Takeichi; Mari Chitose; Hiromi Ohtsubo; Shingo Ishimori; Takeshi Ninchoji; Yuya Hashimura; Hiroshi Kaito; Naoya Morisada; Ichiro Morioka; Hideoki Fukuoka; Masaru Yoshida; Kazumoto Iijima

BACKGROUND A metabolomic approach using umbilical cord blood from infants at birth has not been studied widely yet. AIM We examined changes in metabolite levels in umbilical cord blood at birth via gas chromatography/mass spectrometry (GC/MS)-based metabolomics, with the aim of achieving a detailed understanding of fetal stress during labor. STUDY DESIGN All procedures were reviewed and approved by the Institutional Review Board of Kobe University School of Medicine. This was a cohort study of pregnant women based in Palmore Hospital, which is located in an urban area of Japan, and was carried out between December 2010 and May 2011. SUBJECT Umbilical cord arterial blood samples were obtained from 41 infants immediately after delivery. OUTCOME MEASURES Metabolites in the blood samples were measured using GC/MS to investigate whether the delivery method (spontaneous onset of labor, induction of labor or elective cesarean section) affected the metabolite profile in umbilical cord blood. RESULTS Elective cesarean section without labor led to lower levels of isoleucine, fructose, mannose, glucose, allose, glucuronic acid, inositol and cysteine in comparison with vaginal delivery following spontaneous labor and without medication. CONCLUSION It is proposed that the stress associated with labor be involved in alterations in the levels of metabolites, particularly saccharides such as glucose, in umbilical cord blood.


Nitric Oxide | 2011

Crucial vasculoprotective role of the whole nitric oxide synthase system in vascular lesion formation in mice: Involvement of bone marrow-derived cells.

Yumi Furuno; Tsuyoshi Morishita; Yumiko Toyohira; Sohsuke Yamada; Susumu Ueno; Naoya Morisada; Kazunari Sugita; Katsuhiko Noguchi; Mayuko Sakanashi; Hironori Miyata; Akihide Tanimoto; Yasuyuki Sasaguri; Hiroaki Shimokawa; Yutaka Otsuji; Nobuyuki Yanagihara; Masahito Tamura; Masato Tsutsui

Although all three nitric oxide (NO) synthases (nNOS, iNOS, and eNOS) are expressed in injured arteries, it remains to be elucidated the role of the NOSs in their entirety in the vascular lesion formation. We addressed this issue in mice deficient in all NOS genes. Vascular injury was induced by permanent ligation of a unilateral carotid artery in wild-type (WT), singly, and triply NOS(-/-) mice. Two weeks after the procedure, constrictive vascular remodeling and neointimal formation were recognized in the ligated arteries. While constrictive remodeling was noted in the nNOS(-/-) and iNOS(-/-) genotypes, it was most accelerated in the n/i/eNOS(-/-) genotype. While neointimal formation was evident in the eNOS(-/-) and nNOS(-/-) genotypes, it was also most aggravated in the n/i/eNOS(-/-) genotype. Those lesions were reversed by long-term treatment with isosorbide dinitrate, a NO donor. Finally, we examined the involvement of bone marrow-derived cells in the vascular lesion formation. Bone marrow from the WT, singly, or triply NOS(-/-) mice was transplanted into the WT mice, and then the carotid ligation was performed. Intriguingly, constrictive remodeling and neointimal formation were both similarly most exacerbated in the case of the n/i/eNOS(-/-) bone marrow transplantation. These results indicate that the complete disruption of all the NOS genes causes markedly accelerated vascular lesion formation caused by blood flow disruption in mice in vivo, demonstrating the crucial vasculoprotective role of the whole endogenous NOS system. Our findings also suggest that the NOS system in bone marrow-derived cells may be involved in this vasculoprotective mechanism.


American Journal of Medical Genetics Part A | 2016

A novel PIGN mutation and prenatal diagnosis of inherited glycosylphosphatidylinositol deficiency.

Taku Nakagawa; Mariko Taniguchi-Ikeda; Yoshiko Murakami; Shota Nakamura; Daisuke Motooka; Tomomi Emoto; Wataru Satake; Masahiro Nishiyama; Daisaku Toyoshima; Naoya Morisada; Satoshi Takada; Shinya Tairaku; Nobuhiko Okamoto; Ichiro Morioka; Hiroki Kurahashi; Tatsushi Toda; Taroh Kinoshita; Kazumoto Iijima

Glycosylphosphatidylinositol (GPI) anchors tether proteins to the extracellular face of eukaryotic plasma membranes. Defects in the human GPI anchor biosynthetic pathway cause inherited GPI deficiencies (IGDs) characterized by multiple congenital anomalies: dysmorphic faces, developmental delay, hypotonia, and epilepsy. We report the case of a 6‐year‐old boy with severe psychomotor developmental delay, epilepsy, and decreased granulocyte surface expression of GPI‐anchored protein that suggested autosomal recessive GPI deficiency. The case underwent target exome sequencing to screen for IGDs. Target exome sequencing of the proband identified an apparently homozygous c.808T > C (p.Ser270Pro) mutation in PIGN, a gene involved in the GPI anchor biosynthetic pathway. As his parents were expecting another child, genetic carrier screening was conducted for the parents. Direct sequencing of the parents identified a heterozygous c.808T > C PIGN mutation in the father but none in the mother. To identify the mothers mutation, we performed semi‐quantitative real‐time PCR of the PIGN exons and long PCR, identifying a microdeletion in PIGN (del exons 2–14). The proband had inherited this microdeletion from his mother. Prenatal diagnosis of the fetus revealed that it was a heterozygous carrier of the mothers pathogenic allele. Here, we report a sporadic case of inherited GPI deficiency with a PIGN mutation and the first case of prenatal diagnosis for GPI deficiency.


Brain & Development | 2015

Somatic mosaicism of a CDKL5 mutation identified by next-generation sequencing.

Takeshi Kato; Naoya Morisada; Hiroaki Nagase; Masahiro Nishiyama; Daisaku Toyoshima; Taku Nakagawa; Azusa Maruyama; Xue Jun Fu; Kandai Nozu; Hiroko Wada; Satoshi Takada; Kazumoto Iijima

INTRODUCTION CDKL5-related encephalopathy is an X-linked dominantly inherited disorder that is characterized by early infantile epileptic encephalopathy or atypical Rett syndrome. We describe a 5-year-old Japanese boy with intractable epilepsy, severe developmental delay, and Rett syndrome-like features. Onset was at 2 months, when his electroencephalogram showed sporadic single poly spikes and diffuse irregular poly spikes. METHODS We conducted a genetic analysis using an Illumina® TruSight™ One sequencing panel on a next-generation sequencer. RESULTS We identified two epilepsy-associated single nucleotide variants in our case: CDKL5 p.Ala40Val and KCNQ2 p.Glu515Asp. CDKL5 p.Ala40Val has been previously reported to be responsible for early infantile epileptic encephalopathy. In our case, the CDKL5 heterozygous mutation showed somatic mosaicism because the boys karyotype was 46,XY. The KCNQ2 variant p.Glu515Asp is known to cause benign familial neonatal seizures-1, and this variant showed paternal inheritance. CONCLUSIONS Although we believe that the somatic mosaic CDKL5 mutation is mainly responsible for the neurological phenotype in the patient, the KCNQ2 variant might have some neurological effect. Genetic analysis by next-generation sequencing is capable of identifying multiple variants in a patient.

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Koichi Nakanishi

Wakayama Medical University

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