Mitsuhiro Kato

Yamagata University, Ямагата, Yamagata, Japan

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Publications (91)436.8 Total impact

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    ABSTRACT: Megalencephaly capillary malformation (MCAP) is a syndrome involving brain overgrowth, characterized by megalencephaly, capillary malformations, asymmetric growth, polymicrogyria, polydactyly, and syndactyly. Cerebellar tonsillar herniation (CTH) and ventriculomegaly are also observed in over half the patients with this syndrome. Early sudden death has been reported in MCAP, but its causes and the surgical strategies for its prevention remain unclear. Here, we report on a patient with MCAP who died suddenly at 5 months of age. He presented with progressive macrocephaly and hypotonia. MRI performed at 4 months of age showed tight posterior fossa, bilateral perisylvian polymicrogyria, enlargement of the straight sinus, and a thickened corpus callosum. However, since the patient did not exhibit capillary malformation, polydactyly, or syndactyly, a definitive diagnosis of MCAP could not be made. He died suddenly while asleep at home 1 month later. The sudden death of MCAP patients was previously attributed to CTH, convulsion, or arrhythmia. In this case, progressive cerebellar enlargement appeared to be the underlying cause. After the patient's death, using his preserved DNA, a missense mutation in the AKT3 gene was identified. Vakt murine thymoma viral oncogene homologue (AKT) is a serine-threonine kinase that functions in the mammalian target of rapamycin (mTOR) pathway and plays an important role in cell proliferation. Accurate early diagnosis, including imaging and genetic analyses, and the recognition and treatment of critical conditions are required to prevent the sudden death of patients with MCAP.
    Child s Nervous System 11/2014; · 1.24 Impact Factor
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    ABSTRACT: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by capillary malformation (port-wine stains), and choroidal and leptomeningeal vascular malformations. Previously, the recurrent somatic mutation c.548G>A (p.R183Q) in the G-α q gene (GNAQ) was identified as causative in SWS and non-syndromic port-wine stain patients using whole-genome sequencing. In this study, we investigated somatic mutations in GNAQ by next-generation sequencing. We first performed targeted amplicon sequencing of 15 blood-brain-paired samples in sporadic SWS and identified the recurrent somatic c.548G>A mutation in 80% of patients (12 of 15). The percentage of mutant alleles in brain tissues of these 12 patients ranged from 3.6 to 8.9%. We found no other somatic mutations in any of the seven GNAQ exons in the remaining three patients without c.548G>A. These findings suggest that the recurrent somatic GNAQ mutation c.548G>A is the major determinant genetic factor for SWS and imply that other mutated candidate gene(s) may exist in SWS.Journal of Human Genetics advance online publication, 6 November 2014; doi:10.1038/jhg.2014.95.
    Journal of human genetics. 11/2014;
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    ABSTRACT: Kinesins are a large superfamily of molecular motors. They move along microtubule filaments and are powered by the hydrolysis of ATP. This transport system is essential for neuronal function and survival. KIF1A belongs to the kinesin 3 family and involves in the anterograde transport of synaptic vesicle precursors along axons. Several studies confirmed that KIF1A mutations cause spastic paraplegia and sensory neuropathy in an autosomal-recessive fashion. A missense mutation in the KIF1A gene (p.Thr99Met) has been reported in a patient with intellectual disability (ID), axial hypotonia and peripheral spasticity. Mild atrophy of the cerebellar vermis was found on magnetic resonance imaging. The mutation was heterozygous and de novo. We identified the second patient with the p.T99M mutation in the KIF1A gene by whole-exome sequencing. He showed severe ID, spasticity, optic atrophy, neurogenic bladder, growth failure and progressive cerebellar atrophy. The p.T99M mutation may be a common recurrent mutation. We suppose that this specific mutation of KIF1A shows a novel neurodegenerative syndrome.Journal of Human Genetics advance online publication, 25 September 2014; doi:10.1038/jhg.2014.80.
    Journal of Human Genetics 09/2014; · 2.53 Impact Factor
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    ABSTRACT: Recently, de novo mutations in TBL1XR1 were found in two patients with autism spectrum disorders. Here, we report on a Japanese girl presenting with West syndrome, Rett syndrome-like and autistic features. Her initial development was normal until she developed a series of spasms at 5 months of age. Electroencephalogram at 7 months showed a pattern of hypsarrhythmia, which led to a diagnosis of West syndrome. Stereotypic hand movements appeared at 8 months of age, and autistic features such as deficits in communication, hyperactivity and excitability were observed later, at 4 years and 9 months. Whole exome sequencing of the patient and her parents revealed a de novo TBL1XR1 mutation [c.209 G>A (p.Gly70Asp)] occurring at an evolutionarily conserved amino acid in an F-box-like domain. Our report expands the clinical spectrum of TBL1XR1 mutations to West syndrome with Rett-like features, together with autistic features.Journal of Human Genetics advance online publication, 7 August 2014; doi:10.1038/jhg.2014.71.
    Journal of human genetics. 08/2014;
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    ABSTRACT: We developed a next-generation sequencing(NGS)based mutation screening strategy for neurodevelopmental diseases. Using this system, we screened 284 genes in 40 patients. Several novel mutations were discovered. Patient 1 had a novel mutation in ACTB. Her dysmorphic feature was mild for Baraitser-Winter syndrome. Patient 2 had a truncating mutation of DYRK1A. She lacked microcephaly, which was previously assumed to be a constant feature of DYRK1A loss of function. Patient 3 had a novel mutation in GABRD gene. She showed Rett syndrome like features. Patient 4 was diagnosed with Noonan syndrome with PTPN11 mutation. He showed complete agenesis of corpus callosum. We discussed these novel findings.
    Clinical Genetics 08/2014; · 4.25 Impact Factor
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    ABSTRACT: Background: Adrenocorticotropic hormone (ACTH) therapy is the first-line therapy for infantile spasms, and is effective for many other intractable epilepsies. While spasms may respond to ACTH for weeks, a substantial proportion of patients develop recurrent seizures over a yearly period. To maintain efficacy, we treated two children with intractable epilepsy with weekly ACTH therapy for 1 year and described the changes in clinical seizures, electroencephalograms, developmental assessments and side effects. Subjects and methods: A girl with infantile spasms due to lissencephaly and a boy with atypical absence seizures were studied. In both cases, seizures were frequent and resistant to antiepileptic drugs; electroencephalograms showed continuous epileptiform activities, and the patients’ development was delayed and stagnant prior to ACTH treatment. The initial ACTH therapy (daily 0.015 mg/kg for 2 weeks, 0.015 mg/kg every 2 days for 1 week, 0.0075 mg/kg every 2 days for 1 week), was transiently effective in both cases. The second-round ACTH therapy consisted of the initial ACTH therapy protocol followed by weekly ACTH injections (0.015 mg/kg or 0.0075 mg/kg) for 1 year. Both cases were followed for at least 1 year after therapy. Results: In both patients, clinical seizures were completely controlled during and 1 year after the second-round AHCH therapy. Continuous epileptiform discharges disappeared, while intermittent interictal epileptiform discharges remained. Both patients showed some developmental gains after achieving seizure control. No serious side effects were recorded. Conclusion: Further studies are warranted to determine if a long-term weekly ACTH is a safe and effective treatment for intractable epilepsy.
    Brain and Development 08/2014; · 1.67 Impact Factor
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    ABSTRACT: Recessive mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor synthesis pathway have been demonstrated as causative of GPI deficiency disorders associated with intellectual disability, seizures, and diverse congenital anomalies. We performed whole exome sequencing in a patient with progressive encephalopathies and multiple dysmorphism with hypophosphatasia and identified novel compound heterozygous mutations, c.250G>T (p. Glu84*) and c.1342C>T (p. Arg488Trp), in PIGT encoding a subunit of the GPI transamidase complex. The surface expression of GPI-anchored proteins (GPI-APs) on patient granulocytes was lower than that of healthy controls. Transfection of the Arg488Trp mutant PIGT construct, but not the Glu84* mutant, into PIGT-deficient cells partially restored the expression of GPI-APs DAF and CD59. These results indicate that PIGT mutations caused neurological impairment and multiple congenital anomalies in this patient.
    Neurogenetics 06/2014; · 3.58 Impact Factor
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    ABSTRACT: Objective De novo SCN8A mutations have been reported in patients with epileptic encephalopathy. Herein we report seven patients with de novo heterozygous SCN8A mutations, which were found in our comprehensive genetic analysis (target capture or whole-exome sequencing) for early onset epileptic encephalopathies (EOEEs).MethodsA total of 163 patients with EOEEs without mutations in known genes, including 6 with malignant migrating partial seizures in infancy (MMPSI), and 60 with unclassified EOEEs, were analyzed by target capture (28 samples) or whole-exome sequencing (135 samples).ResultsWe identified de novo SCN8A mutations in 7 patients: 6 of 60 unclassified EOEEs (10.0%), and one of 6 MMPSI cases (16.7%). The mutations were scattered through the entire gene: four mutations were located in linker regions, two in the fourth transmembrane segments, and one in the C-terminal domain. The type of the initial seizures was variable including generalized tonic–clonic, atypical absence, partial, apneic attack, febrile convulsion, and loss of tone and consciousness. Onset of seizures was during the neonatal period in two patients, and between 3 and 7 months of age in five patients. Brain magnetic resonance imaging (MRI) showed cerebellar and cerebral atrophy in one and six patients, respectively. All patients with SCN8A missense mutations showed initially uncontrollable seizures by any drugs, but eventually one was seizure-free and three were controlled at the last examination. All patients showed developmental delay or regression in infancy, resulting in severe intellectual disability.SignificanceOur data reveal that SCN8A mutations can cause variable phenotypes, most of which can be diagnosed as unclassified EOEEs, and rarely as MMPSI. Together with previous reports, our study further indicates that genetic testing of SCN8A should be considered in children with unclassified severe epilepsy.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
    Epilepsia 05/2014; · 3.96 Impact Factor
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    ABSTRACT: To investigate the clinical spectrum caused by mutations in PIGA at Xp22.2, which is involved in the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor, among patients with early-onset epileptic encephalopathies (EOEEs). Whole-exome sequencing was performed as a comprehensive genetic analysis for a cohort of 172 patients with EOEEs including early myoclonic encephalopathy, Ohtahara syndrome, and West syndrome, and PIGA mutations were carefully investigated. We identified 4 PIGA mutations in probands showing early myoclonic encephalopathy, West syndrome, or unclassified EOEE. Flow cytometry of blood granulocytes from patients demonstrated reduced expression of GPI-anchored proteins. Expression of GPI-anchored proteins in PIGA-deficient JY5 cells was only partially or hardly restored by transient expression of PIGA mutants with a weak TATA box promoter, indicating a variable loss of PIGA activity. The phenotypic consequences of PIGA mutations can be classified into 2 types, severe and less severe, which correlate with the degree of PIGA activity reduction caused by the mutations. Severe forms involved myoclonus and asymmetrical suppression bursts on EEG, multiple anomalies with a dysmorphic face, and delayed myelination with restricted diffusion patterns in specific areas. The less severe form presented with intellectual disability and treatable seizures without facial dysmorphism. Our study confirmed that PIGA mutations are one genetic cause of EOEE, suggesting that GPI-anchor deficiencies may be an underlying cause of EOEE.
    Neurology 04/2014; · 8.30 Impact Factor
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    ABSTRACT: Eukaryotic elongation factor 1, alpha-2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G>A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G>C, p.Asp252His and c.364G>A, p.Glu122Lys) in EEF1A2 found by whole exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.
    Clinical Genetics 03/2014; · 4.25 Impact Factor
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    ABSTRACT: Focal cortical dysplasia is a common cortical malformation and an important cause of epilepsy. There is evidence for shared molecular mechanisms underlying cortical dysplasia, ganglioglioma, hemimegalencephaly, and dysembryoplastic neuroepithelial tumor. However, there are no familial reports of typical cortical dysplasia or co-occurrence of cortical dysplasia and related lesions within the same pedigree. We report the clinical, imaging, and histologic features of six pedigrees with familial cortical dysplasia and related lesions. Twelve patients from six pedigrees were ascertained from pediatric and adult epilepsy centers, eleven of whom underwent epilepsy surgery. Pedigree data, clinical information, neuroimaging findings, and histopathologic features are presented. The families comprise brothers with focal cortical dysplasia, a male and his sister with focal cortical dysplasia, a female with focal cortical dysplasia and her brother with hemimegalencephaly, a female with focal cortical dysplasia and her female first cousin with ganglioglioma, a female with focal cortical dysplasia and her male cousin with dysembryoplastic neuroepithelial tumor, and a female and her nephew with focal cortical dysplasia. This series shows that focal cortical dysplasia can be familial and provides clinical evidence suggesting that cortical dysplasia, hemimegalencephaly, ganglioglioma, and dysembryoplastic neuroepithelial tumors may share common genetic determinants.
    Epilepsia 02/2014; · 3.96 Impact Factor
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    ABSTRACT: The hallmark of neuronopathic Gaucher disease (GD) is oculomotor abnormalities, but ophthalmological assessment is difficult in uncooperative patients. Chromatic pupillometry is a quantitative method to assess the pupillary light reflex (PLR) with minimal patient cooperation. Thus, we investigated whether chromatic pupillometry could be useful for neurological evaluations in GD. In our neuronopathic GD patients, red light-induced PLR was markedly impaired, whereas blue light-induced PLR was relatively spared. In addition, patients with non-neuronopathic GD showed no abnormalities. These novel findings show that chromatic pupillometry is a convenient method to detect neurological signs and monitor the course of disease in neuronopathic GD.
    Annals of Clinical and Translational Neurology. 02/2014;
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    ABSTRACT: Objectives. Aicardi-Goutières syndrome (AGS) is a rare, genetically determined, early onset progressive encephalopathy associated with autoimmune manifestations. AGS is usually inherited in an autosomal recessive manner. The disease is rare, therefore the clinical manifestations and genotype-phenotype correlations, particularly with regard to autoimmune diseases, are still unclear. Here we performed a nationwide survey of AGS patients in Japan and analysed the genetic and clinical data.Methods. Patients were recruited via questionnaires sent to paediatric or adult neurologists in Japanese hospitals and institutions. Genetic analysis was performed and clinical data were collected.Results. Fourteen AGS patients were identified from 13 families; 10 harboured genetic mutations. Three patients harboured dominant-type TREX1 mutations. These included two de novo cases: one caused by a novel heterozygous p.His195Tyr mutation and the other by a novel somatic mosaicism resulting in a p.Asp200Asn mutation. Chilblain lesions were observed in all patients harbouring dominant-type TREX1 mutations. All three patients harbouring SAMHD1 mutations were diagnosed with autoimmune diseases, two with SLE and one with SS. The latter is the first reported case.Conclusion. This study is the first to report a nationwide AGS survey, which identified more patients with sporadic AGS carrying de novo dominant-type TREX1 mutations than expected. There was a strong association between the dominant-type TREX1 mutations and chilblain lesions, and between SAMHD1 mutations and autoimmunity. These findings suggest that rheumatologists should pay attention to possible sporadic AGS cases presenting with neurological disorders and autoimmune manifestations.
    Rheumatology (Oxford, England) 12/2013; · 4.24 Impact Factor
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    ABSTRACT: Early onset epileptic encephalopathies (EOEE) are severe neurological disorders characterized by frequent seizures accompanied by developmental regression or retardation. Whole-exome sequencing of 12 patients together with five pairs of parents and subsequent Sanger sequencing in additional 328 EOEE patients identified two de novo frameshift and one missense mutations in SLC35A2 at Xp11.23, respectively. The three patients are all females. X-inactivation analysis of blood leukocyte DNA and mRNA analysis using lymphoblastoid cells derived from two patients with a frameshift mutation indicated that only the wild-type SLC35A2 allele was expressed in these cell types, at least in part likely as a consequence of skewed X-inactivation. SLC35A2 encodes a UDP-galactose transporter, which selectively supplies UDP-galactose from the cytosol to the Golgi lumen. Transient expression experiments revealed that the missense mutant protein was correctly localized in the Golgi apparatus. In contrast, the two frameshift mutant proteins were not properly expressed, suggesting that their function is severely impaired. Defects in the UDP-galactose transporter can cause congenital disorders of glycosylation. Of note, no abnormalities of glycosylation were observed in three serum glycoproteins, which is consistent with favorably skewed X-inactivation. We hypothesize that a substantial number of neurons might express the mutant SLC35A2 allele and suffer from defective galactosylation, resulting in EOEE. This article is protected by copyright. All rights reserved.
    Human Mutation 09/2013; · 5.21 Impact Factor
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    ABSTRACT: This report describes a male case of subcortical band heterotopia (SBH) with somatic mosaicism of doublecortin (DCX) mutation. His brain MRI revealed bilateral SBH with anterior dominant pachygyria. Although he had infantile spasms from 5-months old and showed mild developmental delay, he responded well to vitamin B6 and ACTH therapy. We conducted DCX mutation analysis using peripheral blood lymphocytes of the proband and his parents. Only the present case showed the mixture pattern of missense mutation (c. 167 G>C) and normal sequence of DCX gene indicating that the present case resulted from somatic mosaicism of de novo DCX mutation. Male patients with DCX mutations generally present with the classical type of lissencephaly, severe developmental delay, and intractable epilepsy. However, somatic mosaic mutation of DCX can lead to SBH in males.
    No to hattatsu. Brain and development 09/2013; 45(5):371-4.
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    ABSTRACT: Here we report a case of a 10-year-old female with unclassified epileptic encephalopathy who showed forced normalization after administration of levetiracetam (LEV). She initially presented with intractable tonic and myoclonic seizures that were observed about 10 times a day along with frequent multifocal sharp and slow wave complexes on electroencephalography (EEG). We were forced to decrease the topiramate dose because of the appearance of nystagmus, and her myoclonic seizures became worse. We added LEV (250 mg/day) and her tonic and myoclonic seizures disappeared one day after initiation of LEV administration. However, she showed hyporesponsiveness and akinesia. The disappearance of paroxysmal discharges on EEG confirmed the diagnosis of forced normalization. Despite continuous administration of LEV, tonic and myoclonic seizures relapsed within a month but her psychotic symptoms resolved simultaneously. To the best of our knowledge, this is the first reported case of forced normalization after LEV administration. It should be noted that LEV may cause forced normalization although it can be started at an adequate dosage.
    No to hattatsu. Brain and development 09/2013; 45(5):375-8.
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    ABSTRACT: Heterotrimeric G proteins, composed of α, β, and γ subunits, can transduce a variety of signals from seven-transmembrane-type receptors to intracellular effectors. By whole-exome sequencing and subsequent mutation screening, we identified de novo heterozygous mutations in GNAO1, which encodes a Gαo subunit of heterotrimeric G proteins, in four individuals with epileptic encephalopathy. Two of the affected individuals also showed involuntary movements. Somatic mosaicism (approximately 35% to 50% of cells, distributed across multiple cell types, harbored the mutation) was shown in one individual. By mapping the mutation onto three-dimensional models of the Gα subunit in three different complexed states, we found that the three mutants (c.521A>G [p.Asp174Gly], c.836T>A [p.Ile279Asn], and c.572_592del [p.Thr191_Phe197del]) are predicted to destabilize the Gα subunit fold. A fourth mutant (c.607G>A), in which the Gly203 residue located within the highly conserved switch II region is substituted to Arg, is predicted to impair GTP binding and/or activation of downstream effectors, although the p.Gly203Arg substitution might not interfere with Gα binding to G-protein-coupled receptors. Transient-expression experiments suggested that localization to the plasma membrane was variably impaired in the three putatively destabilized mutants. Electrophysiological analysis showed that Gαo-mediated inhibition of calcium currents by norepinephrine tended to be lower in three of the four Gαo mutants. These data suggest that aberrant Gαo signaling can cause multiple neurodevelopmental phenotypes, including epileptic encephalopathy and involuntary movements.
    The American Journal of Human Genetics 08/2013; · 11.20 Impact Factor
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    ABSTRACT: We aimed to investigate the possible association between SCN2A mutations and early-onset epileptic encephalopathies (EOEEs). We recruited a total of 328 patients with EOEE, including 67 patients with Ohtahara syndrome (OS) and 150 with West syndrome. SCN2A mutations were examined using high resolution melt analysis or whole exome sequencing. We found 14 novel SCN2A missense mutations in 15 patients: 9 of 67 OS cases (13.4%), 1 of 150 West syndrome cases (0.67%), and 5 of 111 with unclassified EOEEs (4.5%). Twelve of the 14 mutations were confirmed as de novo, and all mutations were absent in 212 control exomes. A de novo mosaic mutation (c.3976G>C) with a mutant allele frequency of 18% was detected in one patient. One mutation (c.634A>G) was found in transcript variant 3, which is a neonatal isoform. All 9 mutations in patients with OS were located in linker regions between 2 transmembrane segments. In 7 of the 9 patients with OS, EEG findings transitioned from suppression-burst pattern to hypsarrhythmia. All 15 of the patients with novel SCN2A missense mutations had intractable seizures; 3 of them were seizure-free at the last medical examination. All patients showed severe developmental delay. Our study confirmed that SCN2A mutations are an important genetic cause of OS. Given the wide clinical spectrum associated with SCN2A mutations, genetic testing for SCN2A should be considered for children with different epileptic conditions.
    Neurology 08/2013; · 8.30 Impact Factor
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    ABSTRACT: Kabuki syndrome is a congenital anomaly syndrome characterized by developmental delay, intellectual disability, specific facial features including long palpebral fissures and ectropion of the lateral third of the lower eyelids, prominent digit pads, and skeletal and visceral abnormalities. Mutations in MLL2 and KDM6A cause Kabuki syndrome. We screened 81 individuals with Kabuki syndrome for mutations in these genes by conventional methods (n = 58) and/or targeted resequencing (n = 45) or whole exome sequencing (n = 5). We identified a mutation in MLL2 or KDM6A in 50 (61.7%) and 5 (6.2%) cases, respectively. Thirty-five MLL2 mutations and two KDM6A mutations were novel. Non-protein truncating-type MLL2 mutations were mainly located around functional domains, while truncating-type mutations were scattered through the entire coding region. The facial features of patients in the MLL2 truncating-type mutation group were typical based on those of the 10 originally reported patients with Kabuki syndrome; those of the other groups were less typical. High arched eyebrows, short fifth finger, and hypotonia in infancy were more frequent in the MLL2 mutation group than in the KDM6A mutation group. Short stature and postnatal growth retardation were observed in all individuals with KDM6A mutations, but in only half of the group with MLL2 mutations. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 08/2013; · 2.30 Impact Factor
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    ABSTRACT: Background: There have been numerous reports regarding serum or cerebrospinal fluid (CSF) biomarkers in various disorders; however, the validities of such biomarkers for more precise diagnoses and prognosis estimates remain to be determined, especially in pediatric patients with neurological disorders. Methods: Serum/CSF S100B, neuron-specific enolase, and total tau (tTau) were measured in various acute pediatric neurological disorders, and their usefulness for diagnostic and prognostic predictions was validated using receiver operating characteristic curves and area under the curve (AUC) analysis. Results: A total of 336 serum and 200 CSF specimens from 313 patients were examined, and we identified statistically significant differences that were relevant from diagnostic and prognostic viewpoints. CSF and serum tTau levels could be good predictors for diagnosis (CSF tTau; AUC=0.76) and prognosis (serum tTau; AUC=0.78). Conclusions: Both CSF and serum tTau levels could be useful for precise diagnostic and prognostic estimations in acute pediatric neurological disorders. Further studies are needed to clarify the clinical significance of such biomarkers.
    Brain & development 07/2013; · 1.74 Impact Factor

Publication Stats

2k Citations
436.80 Total Impact Points


  • 2002–2014
    • Yamagata University
      • Department of Pediatrics
      Ямагата, Yamagata, Japan
  • 2013
    • Gunma Children's Medical Center
      Shibukawa, Gunma Prefecture, Japan
    • University of Fukui
      • Division of Pediatrics
      Hukui, Fukui, Japan
    • Shinshu University
      • Department of Medical Genetics
      Shonai, Nagano, Japan
  • 2008–2013
    • Yokohama City University
      Yokohama, Kanagawa, Japan
    • National Center for Child Health and Development
      Edo, Tōkyō, Japan
  • 2007
    • Yamagata Prefectural Central Hospital
      Ямагата, Yamagata, Japan
    • Niigata University
      • Division of Neurosurgery
      Niahi-niigata, Niigata, Japan
  • 2005
    • Kanagawa Children's Medical Center
      Yokohama, Kanagawa, Japan
  • 2002–2004
    • University of Chicago
      • Department of Human Genetics
      Chicago, IL, United States