Amelioration of a neurodevelopmental disorder by carbamazepine in a case having a gain-of-function GRIA3 variant View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-01-15

AUTHORS

Kohei Hamanaka, Keita Miyoshi, Jia-Hui Sun, Keisuke Hamada, Takao Komatsubara, Ken Saida, Naomi Tsuchida, Yuri Uchiyama, Atsushi Fujita, Takeshi Mizuguchi, Benedicte Gerard, Allan Bayat, Berardo Rinaldi, Mitsuhiro Kato, Jun Tohyama, Kazuhiro Ogata, Yun Stone Shi, Kuniaki Saito, Satoko Miyatake, Naomichi Matsumoto

ABSTRACT

GRIA3 at Xq25 encodes glutamate ionotropic receptor AMPA type 3 (GluA3), a subunit of postsynaptic glutamate-gated ion channels mediating neurotransmission. Hemizygous loss-of-function (LOF) variants in GRIA3 cause a neurodevelopmental disorder (NDD) in male individuals. Here, we report a gain-of-function (GOF) variant at GRIA3 in a male patient. We identified a hemizygous de novo missense variant in GRIA3 in a boy with an NDD: c.1844C > T (p.Ala615Val) using whole-exome sequencing. His neurological signs, such as hypertonia and hyperreflexia, were opposite to those in previous cases having LOF GRIA3 variants. His seizures and hypertonia were ameliorated by carbamazepine, inhibiting glutamate release from presynapses. Patch-clamp recordings showed that the human GluA3 mutant (p.Ala615Val) had slower desensitization and deactivation kinetics. A fly line expressing a human GluA3 mutant possessing our variant and the Lurcher variant, which makes ion channels leaky, showed developmental defects, while one expressing a mutant possessing either of them did not. Collectively, these results suggest that p.Ala615Val has GOF effects. GRIA3 GOF variants may cause an NDD phenotype distinctive from that of LOF variants, and drugs suppressing glutamatergic neurotransmission may ameliorate this phenotype. This study should help in refining the clinical management of GRIA3-related NDDs. More... »

PAGES

283-293

References to SciGraph publications

  • 2015-11-05. Effects of Levetiracetam, Carbamazepine, Phenytoin, Valproate, Lamotrigine, Oxcarbazepine, Topiramate, Vinpocetine and Sertraline on Presynaptic Hippocampal Na+ and Ca2+ Channels Permeability in NEUROCHEMICAL RESEARCH
  • 2010-04. A method and server for predicting damaging missense mutations in NATURE METHODS
  • 1993-01. A synaptic model of memory: long-term potentiation in the hippocampus in NATURE
  • 2015-03-05. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology in GENETICS IN MEDICINE
  • 2013-07-11. Neuronal necrosis and spreading death in a Drosophila genetic model in CELL DEATH & DISEASE
  • 2020-03-17. Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders in GENOME MEDICINE
  • 2016-04-15. Synaptic AMPA receptor composition in development, plasticity and disease in NATURE REVIEWS NEUROSCIENCE
  • 2014-04-11. X-exome sequencing in Finnish families with Intellectual Disability - four novel mutations and two novel syndromic phenotypes in ORPHANET JOURNAL OF RARE DISEASES
  • 2015-08-21. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals in NATURE COMMUNICATIONS
  • 2010-08. MutationTaster evaluates disease-causing potential of sequence alterations in NATURE METHODS
  • 2017-06-19. Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains in NATURE NEUROSCIENCE
  • 1997-08. Neurodegeneration in Lurcher mice caused by mutation in δ2 glutamate receptor gene in NATURE
  • 2009-06-25. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm in NATURE PROTOCOLS
  • 2020-10-10. Novel EXOSC9 variants cause pontocerebellar hypoplasia type 1D with spinal motor neuronopathy and cerebellar atrophy in JOURNAL OF HUMAN GENETICS
  • 2008-03-02. Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes in NATURE GENETICS
  • 2017-07-24. Channel opening and gating mechanism in AMPA-subtype glutamate receptors in NATURE
  • 2020-05-27. The mutational constraint spectrum quantified from variation in 141,456 humans in NATURE
  • 2016-02-25. Human genetic variation database, a reference database of genetic variations in the Japanese population in JOURNAL OF HUMAN GENETICS
  • 2015-12-08. Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia in JOURNAL OF NEUROLOGY
  • Journal

    TITLE

    Human Genetics

    ISSUE

    2

    VOLUME

    141

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00439-021-02416-7

    DOI

    http://dx.doi.org/10.1007/s00439-021-02416-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1144686127

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35031858


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1109", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Neurosciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acid Substitution", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals, Genetically Modified", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Carbamazepine", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Child, Preschool", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drosophila melanogaster", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Excitatory Amino Acid Antagonists", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gain of Function Mutation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "HEK293 Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutant Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutation, Missense", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neurodevelopmental Disorders", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Patch-Clamp Techniques", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Phenotype", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptors, AMPA", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Recombinant Proteins", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.268441.d", 
              "name": [
                "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hamanaka", 
            "givenName": "Kohei", 
            "id": "sg:person.0777321437.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0777321437.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Invertebrate Genetics, Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan", 
              "id": "http://www.grid.ac/institutes/grid.275033.0", 
              "name": [
                "Invertebrate Genetics Laboratory, Department of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan", 
                "Division of Invertebrate Genetics, Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Miyoshi", 
            "givenName": "Keita", 
            "id": "sg:person.01226075705.36", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01226075705.36"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China", 
              "id": "http://www.grid.ac/institutes/grid.41156.37", 
              "name": [
                "Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Sun", 
            "givenName": "Jia-Hui", 
            "id": "sg:person.010027005677.62", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010027005677.62"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.268441.d", 
              "name": [
                "Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hamada", 
            "givenName": "Keisuke", 
            "id": "sg:person.014257250371.26", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014257250371.26"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Child Neurology, NHO Nishiniigata Chuo Hospital, Niigata, Niigata, Japan", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Department of Child Neurology, NHO Nishiniigata Chuo Hospital, Niigata, Niigata, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Komatsubara", 
            "givenName": "Takao", 
            "id": "sg:person.013065235571.92", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013065235571.92"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.268441.d", 
              "name": [
                "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Saida", 
            "givenName": "Ken", 
            "id": "sg:person.0771632630.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0771632630.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.470126.6", 
              "name": [
                "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
                "Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tsuchida", 
            "givenName": "Naomi", 
            "id": "sg:person.010452633515.16", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010452633515.16"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.470126.6", 
              "name": [
                "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
                "Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Uchiyama", 
            "givenName": "Yuri", 
            "id": "sg:person.01227034056.86", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01227034056.86"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.268441.d", 
              "name": [
                "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fujita", 
            "givenName": "Atsushi", 
            "id": "sg:person.0665566724.29", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0665566724.29"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.268441.d", 
              "name": [
                "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mizuguchi", 
            "givenName": "Takeshi", 
            "id": "sg:person.01213474560.37", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01213474560.37"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratoires de Diagnostic G\u00e9n\u00e9tique, Institut Medical d\u2019Alsace, H\u00f4pitaux Universitaire de Strasbourg, Strasbourg, France", 
              "id": "http://www.grid.ac/institutes/grid.412220.7", 
              "name": [
                "Laboratoires de Diagnostic G\u00e9n\u00e9tique, Institut Medical d\u2019Alsace, H\u00f4pitaux Universitaire de Strasbourg, Strasbourg, France"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gerard", 
            "givenName": "Benedicte", 
            "id": "sg:person.01204506642.82", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01204506642.82"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute for Regional Health Services Research, University of Southern Denmark, Odense, Denmark", 
              "id": "http://www.grid.ac/institutes/grid.10825.3e", 
              "name": [
                "Department for Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark", 
                "Institute for Regional Health Services Research, University of Southern Denmark, Odense, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bayat", 
            "givenName": "Allan", 
            "id": "sg:person.01152453333.59", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01152453333.59"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy", 
              "id": "http://www.grid.ac/institutes/grid.414818.0", 
              "name": [
                "Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rinaldi", 
            "givenName": "Berardo", 
            "id": "sg:person.01011242157.36", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01011242157.36"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan", 
              "id": "http://www.grid.ac/institutes/grid.410714.7", 
              "name": [
                "Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kato", 
            "givenName": "Mitsuhiro", 
            "id": "sg:person.014500613032.37", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014500613032.37"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Niigata University Medical and Dental Hospital, Niigata, Niigata, Japan", 
              "id": "http://www.grid.ac/institutes/grid.412181.f", 
              "name": [
                "Department of Child Neurology, NHO Nishiniigata Chuo Hospital, Niigata, Niigata, Japan", 
                "Niigata University Medical and Dental Hospital, Niigata, Niigata, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tohyama", 
            "givenName": "Jun", 
            "id": "sg:person.01112357030.87", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01112357030.87"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.268441.d", 
              "name": [
                "Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ogata", 
            "givenName": "Kazuhiro", 
            "id": "sg:person.0737306417.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0737306417.00"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China", 
              "id": "http://www.grid.ac/institutes/grid.41156.37", 
              "name": [
                "Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Shi", 
            "givenName": "Yun Stone", 
            "id": "sg:person.01161402433.96", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01161402433.96"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Invertebrate Genetics, Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan", 
              "id": "http://www.grid.ac/institutes/grid.275033.0", 
              "name": [
                "Invertebrate Genetics Laboratory, Department of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan", 
                "Division of Invertebrate Genetics, Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Saito", 
            "givenName": "Kuniaki", 
            "id": "sg:person.01324346645.35", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01324346645.35"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.470126.6", 
              "name": [
                "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
                "Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Miyatake", 
            "givenName": "Satoko", 
            "id": "sg:person.0661323161.22", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0661323161.22"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan", 
              "id": "http://www.grid.ac/institutes/grid.268441.d", 
              "name": [
                "Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Matsumoto", 
            "givenName": "Naomichi", 
            "id": "sg:person.01020376771.12", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01020376771.12"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/s10038-020-00853-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1131567574", 
              "https://doi.org/10.1038/s10038-020-00853-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/jhg.2016.12", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016186613", 
              "https://doi.org/10.1038/jhg.2016.12"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00415-015-7984-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050069422", 
              "https://doi.org/10.1007/s00415-015-7984-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms9018", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029523624", 
              "https://doi.org/10.1038/ncomms9018"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/42009", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042789897", 
              "https://doi.org/10.1038/42009"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2009.86", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015642657", 
              "https://doi.org/10.1038/nprot.2009.86"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/361031a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042608618", 
              "https://doi.org/10.1038/361031a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1750-1172-9-49", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032812490", 
              "https://doi.org/10.1186/1750-1172-9-49"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nn.4589", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1086070786", 
              "https://doi.org/10.1038/nn.4589"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.101", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001071534", 
              "https://doi.org/10.1038/ng.101"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature23479", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1090859634", 
              "https://doi.org/10.1038/nature23479"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41586-020-2308-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1127885244", 
              "https://doi.org/10.1038/s41586-020-2308-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/gim.2015.30", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022229472", 
              "https://doi.org/10.1038/gim.2015.30"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth0810-575", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028459136", 
              "https://doi.org/10.1038/nmeth0810-575"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cddis.2013.232", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031461285", 
              "https://doi.org/10.1038/cddis.2013.232"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth0410-248", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007489634", 
              "https://doi.org/10.1038/nmeth0410-248"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrn.2016.37", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025635946", 
              "https://doi.org/10.1038/nrn.2016.37"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s11064-015-1749-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019509142", 
              "https://doi.org/10.1007/s11064-015-1749-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13073-020-00725-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1125709453", 
              "https://doi.org/10.1186/s13073-020-00725-6"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2022-01-15", 
        "datePublishedReg": "2022-01-15", 
        "description": "GRIA3 at Xq25 encodes glutamate ionotropic receptor AMPA type 3 (GluA3), a subunit of postsynaptic glutamate-gated ion channels mediating neurotransmission. Hemizygous loss-of-function (LOF) variants in GRIA3 cause a neurodevelopmental disorder (NDD) in male individuals. Here, we report a gain-of-function (GOF) variant at GRIA3 in a male patient. We identified a hemizygous de novo missense variant in GRIA3 in a boy with an NDD: c.1844C\u2009>\u2009T (p.Ala615Val) using whole-exome sequencing. His neurological signs, such as hypertonia and hyperreflexia, were opposite to those in previous cases having LOF GRIA3 variants. His seizures and hypertonia were ameliorated by carbamazepine, inhibiting glutamate release from presynapses. Patch-clamp recordings showed that the human GluA3 mutant (p.Ala615Val) had slower desensitization and deactivation kinetics. A fly line expressing a human GluA3 mutant possessing our variant and the Lurcher variant, which makes ion channels leaky, showed developmental defects, while one expressing a mutant possessing either of them did not. Collectively, these results suggest that p.Ala615Val has GOF effects. GRIA3 GOF variants may cause an NDD phenotype distinctive from that of LOF variants, and drugs suppressing glutamatergic neurotransmission may ameliorate this phenotype. This study should help in refining the clinical management of GRIA3-related NDDs.", 
        "genre": "article", 
        "id": "sg:pub.10.1007/s00439-021-02416-7", 
        "isAccessibleForFree": false, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.9198895", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.9208415", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.5557423", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.9207919", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.9208923", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1085982", 
            "issn": [
              "0340-6717", 
              "1432-1203"
            ], 
            "name": "Human Genetics", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "2", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "141"
          }
        ], 
        "keywords": [
          "neurodevelopmental disorders", 
          "function variants", 
          "glutamate-gated ion channels", 
          "patch-clamp recordings", 
          "novo missense variants", 
          "whole-exome sequencing", 
          "ion channels", 
          "male patients", 
          "glutamate release", 
          "neurological signs", 
          "glutamatergic neurotransmission", 
          "clinical management", 
          "slow desensitization", 
          "GOF effects", 
          "GOF variants", 
          "LoF variants", 
          "missense variants", 
          "type 3", 
          "hemizygous loss", 
          "hypertonia", 
          "GRIA3", 
          "previous cases", 
          "neurotransmission", 
          "male individuals", 
          "disorders", 
          "carbamazepine", 
          "developmental defects", 
          "phenotype", 
          "hyperreflexia", 
          "patients", 
          "seizures", 
          "variants", 
          "deactivation kinetics", 
          "presynapses", 
          "desensitization", 
          "drugs", 
          "NDD phenotype", 
          "amelioration", 
          "cases", 
          "boys", 
          "signs", 
          "recordings", 
          "individuals", 
          "release", 
          "management", 
          "sequencing", 
          "study", 
          "defects", 
          "gain", 
          "loss", 
          "effect", 
          "subunits", 
          "mutants", 
          "lines", 
          "results", 
          "fly lines", 
          "channels", 
          "kinetics"
        ], 
        "name": "Amelioration of a neurodevelopmental disorder by carbamazepine in a case having a gain-of-function GRIA3 variant", 
        "pagination": "283-293", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1144686127"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1007/s00439-021-02416-7"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "35031858"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1007/s00439-021-02416-7", 
          "https://app.dimensions.ai/details/publication/pub.1144686127"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-11-24T21:09", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221124/entities/gbq_results/article/article_956.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1007/s00439-021-02416-7"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00439-021-02416-7'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00439-021-02416-7'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00439-021-02416-7'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00439-021-02416-7'


     

    This table displays all metadata directly associated to this object as RDF triples.

    445 TRIPLES      21 PREDICATES      120 URIs      93 LITERALS      25 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1007/s00439-021-02416-7 schema:about N01494a89c2ff426598c83f0c332f3617
    2 N049aabe99a724d3899113f5ceb4ba821
    3 N04e9250d67514495867f5cf6ada461c5
    4 N23ba6f7165e444f695ebdf57bad90248
    5 N27dfaf0236c042a4b30a68ba0919fe10
    6 N2c624cefb7dd47f5846e323dfa9cafd9
    7 N5803aac180e94e1e824de8db072e0b29
    8 N67a325c02d9f4ecf9c9ba03bdc8f7372
    9 N68bf8e4c503a43799c788c81df193fbc
    10 N6a6ccd92a3674d8d84e7429680d7546b
    11 N85a6378dc14949718e4e5ba59e4094d1
    12 N88a1d1fb85244890a79150188dceb1be
    13 N88a206ad7dd84a549060f9465aab94a0
    14 N9c811f1feeeb4ed5a792f4330f465f84
    15 Ncf2a23280c534632a23e9a0f7754da34
    16 Ndd76ce85f2de4bd2b95364b22c73c858
    17 Ne2709102147f40d1b350a6352b86c801
    18 Nf0532e8d0de947b3b9384c4a01302e64
    19 anzsrc-for:11
    20 anzsrc-for:1109
    21 schema:author N3f956db2e74f4208ad69c69fcf0724d4
    22 schema:citation sg:pub.10.1007/s00415-015-7984-0
    23 sg:pub.10.1007/s11064-015-1749-0
    24 sg:pub.10.1038/361031a0
    25 sg:pub.10.1038/42009
    26 sg:pub.10.1038/cddis.2013.232
    27 sg:pub.10.1038/gim.2015.30
    28 sg:pub.10.1038/jhg.2016.12
    29 sg:pub.10.1038/nature23479
    30 sg:pub.10.1038/ncomms9018
    31 sg:pub.10.1038/ng.101
    32 sg:pub.10.1038/nmeth0410-248
    33 sg:pub.10.1038/nmeth0810-575
    34 sg:pub.10.1038/nn.4589
    35 sg:pub.10.1038/nprot.2009.86
    36 sg:pub.10.1038/nrn.2016.37
    37 sg:pub.10.1038/s10038-020-00853-2
    38 sg:pub.10.1038/s41586-020-2308-7
    39 sg:pub.10.1186/1750-1172-9-49
    40 sg:pub.10.1186/s13073-020-00725-6
    41 schema:datePublished 2022-01-15
    42 schema:datePublishedReg 2022-01-15
    43 schema:description GRIA3 at Xq25 encodes glutamate ionotropic receptor AMPA type 3 (GluA3), a subunit of postsynaptic glutamate-gated ion channels mediating neurotransmission. Hemizygous loss-of-function (LOF) variants in GRIA3 cause a neurodevelopmental disorder (NDD) in male individuals. Here, we report a gain-of-function (GOF) variant at GRIA3 in a male patient. We identified a hemizygous de novo missense variant in GRIA3 in a boy with an NDD: c.1844C > T (p.Ala615Val) using whole-exome sequencing. His neurological signs, such as hypertonia and hyperreflexia, were opposite to those in previous cases having LOF GRIA3 variants. His seizures and hypertonia were ameliorated by carbamazepine, inhibiting glutamate release from presynapses. Patch-clamp recordings showed that the human GluA3 mutant (p.Ala615Val) had slower desensitization and deactivation kinetics. A fly line expressing a human GluA3 mutant possessing our variant and the Lurcher variant, which makes ion channels leaky, showed developmental defects, while one expressing a mutant possessing either of them did not. Collectively, these results suggest that p.Ala615Val has GOF effects. GRIA3 GOF variants may cause an NDD phenotype distinctive from that of LOF variants, and drugs suppressing glutamatergic neurotransmission may ameliorate this phenotype. This study should help in refining the clinical management of GRIA3-related NDDs.
    44 schema:genre article
    45 schema:isAccessibleForFree false
    46 schema:isPartOf N4586ee3a3ebf43969915a941db912a7b
    47 Nd9f72fcd3b494f178b3f34f50b3f7dd2
    48 sg:journal.1085982
    49 schema:keywords GOF effects
    50 GOF variants
    51 GRIA3
    52 LoF variants
    53 NDD phenotype
    54 amelioration
    55 boys
    56 carbamazepine
    57 cases
    58 channels
    59 clinical management
    60 deactivation kinetics
    61 defects
    62 desensitization
    63 developmental defects
    64 disorders
    65 drugs
    66 effect
    67 fly lines
    68 function variants
    69 gain
    70 glutamate release
    71 glutamate-gated ion channels
    72 glutamatergic neurotransmission
    73 hemizygous loss
    74 hyperreflexia
    75 hypertonia
    76 individuals
    77 ion channels
    78 kinetics
    79 lines
    80 loss
    81 male individuals
    82 male patients
    83 management
    84 missense variants
    85 mutants
    86 neurodevelopmental disorders
    87 neurological signs
    88 neurotransmission
    89 novo missense variants
    90 patch-clamp recordings
    91 patients
    92 phenotype
    93 presynapses
    94 previous cases
    95 recordings
    96 release
    97 results
    98 seizures
    99 sequencing
    100 signs
    101 slow desensitization
    102 study
    103 subunits
    104 type 3
    105 variants
    106 whole-exome sequencing
    107 schema:name Amelioration of a neurodevelopmental disorder by carbamazepine in a case having a gain-of-function GRIA3 variant
    108 schema:pagination 283-293
    109 schema:productId N013daafd5f0f45e2abeabc328b1cc84b
    110 N8bccf96f169b401f94bdaf2a04a13cba
    111 N947d891043564b6d942609f92aad0f3c
    112 schema:sameAs https://app.dimensions.ai/details/publication/pub.1144686127
    113 https://doi.org/10.1007/s00439-021-02416-7
    114 schema:sdDatePublished 2022-11-24T21:09
    115 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    116 schema:sdPublisher N041208f9d7a8484fa4d701394b127f2c
    117 schema:url https://doi.org/10.1007/s00439-021-02416-7
    118 sgo:license sg:explorer/license/
    119 sgo:sdDataset articles
    120 rdf:type schema:ScholarlyArticle
    121 N013daafd5f0f45e2abeabc328b1cc84b schema:name dimensions_id
    122 schema:value pub.1144686127
    123 rdf:type schema:PropertyValue
    124 N01494a89c2ff426598c83f0c332f3617 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    125 schema:name Excitatory Amino Acid Antagonists
    126 rdf:type schema:DefinedTerm
    127 N041208f9d7a8484fa4d701394b127f2c schema:name Springer Nature - SN SciGraph project
    128 rdf:type schema:Organization
    129 N049aabe99a724d3899113f5ceb4ba821 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    130 schema:name Amino Acid Substitution
    131 rdf:type schema:DefinedTerm
    132 N04e9250d67514495867f5cf6ada461c5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    133 schema:name Gain of Function Mutation
    134 rdf:type schema:DefinedTerm
    135 N0d9643aeb75343b096fcea0166937484 rdf:first sg:person.01152453333.59
    136 rdf:rest N79573f6bd4354d20b9d59d3bc87fc5f4
    137 N150096af0de24f4492896f8e44548321 rdf:first sg:person.0737306417.00
    138 rdf:rest N784b2c6a18ae4727a60923f0d6fc2a36
    139 N1d823fdbbefb448cb093402867c516dc rdf:first sg:person.010452633515.16
    140 rdf:rest N3ea9cf9169da4b70a6fde4f4afe4e39b
    141 N23ba6f7165e444f695ebdf57bad90248 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    142 schema:name Carbamazepine
    143 rdf:type schema:DefinedTerm
    144 N27dfaf0236c042a4b30a68ba0919fe10 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    145 schema:name Patch-Clamp Techniques
    146 rdf:type schema:DefinedTerm
    147 N2a47bb5c0b694c509c4da74d2fbf8232 rdf:first sg:person.01204506642.82
    148 rdf:rest N0d9643aeb75343b096fcea0166937484
    149 N2c624cefb7dd47f5846e323dfa9cafd9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Male
    151 rdf:type schema:DefinedTerm
    152 N3ea9cf9169da4b70a6fde4f4afe4e39b rdf:first sg:person.01227034056.86
    153 rdf:rest Nd4b1dcaac47b4a5085eec26a320e9d2f
    154 N3f956db2e74f4208ad69c69fcf0724d4 rdf:first sg:person.0777321437.45
    155 rdf:rest Nfa5f8b1b5d35440d8f522c567bc7f00e
    156 N4586ee3a3ebf43969915a941db912a7b schema:issueNumber 2
    157 rdf:type schema:PublicationIssue
    158 N46fd106dfd8043b28922faca0277f599 rdf:first sg:person.01213474560.37
    159 rdf:rest N2a47bb5c0b694c509c4da74d2fbf8232
    160 N5803aac180e94e1e824de8db072e0b29 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    161 schema:name Animals
    162 rdf:type schema:DefinedTerm
    163 N67a325c02d9f4ecf9c9ba03bdc8f7372 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    164 schema:name Animals, Genetically Modified
    165 rdf:type schema:DefinedTerm
    166 N68bf8e4c503a43799c788c81df193fbc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    167 schema:name Receptors, AMPA
    168 rdf:type schema:DefinedTerm
    169 N6a6ccd92a3674d8d84e7429680d7546b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    170 schema:name Child, Preschool
    171 rdf:type schema:DefinedTerm
    172 N710817e393c543cebde9520aee0b1aee rdf:first sg:person.014257250371.26
    173 rdf:rest N78627ac5d00e498b9c583d93312971ce
    174 N784b2c6a18ae4727a60923f0d6fc2a36 rdf:first sg:person.01161402433.96
    175 rdf:rest Nbae992f5dabc4fc9883d85bbb90448ed
    176 N78627ac5d00e498b9c583d93312971ce rdf:first sg:person.013065235571.92
    177 rdf:rest Ndd126bee709647b280da0b3419a184a4
    178 N79573f6bd4354d20b9d59d3bc87fc5f4 rdf:first sg:person.01011242157.36
    179 rdf:rest Nfe6af74b0a3b4df59d399b57fe0bc5e2
    180 N85a6378dc14949718e4e5ba59e4094d1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    181 schema:name Recombinant Proteins
    182 rdf:type schema:DefinedTerm
    183 N88a1d1fb85244890a79150188dceb1be schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    184 schema:name Neurodevelopmental Disorders
    185 rdf:type schema:DefinedTerm
    186 N88a206ad7dd84a549060f9465aab94a0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    187 schema:name HEK293 Cells
    188 rdf:type schema:DefinedTerm
    189 N8bccf96f169b401f94bdaf2a04a13cba schema:name pubmed_id
    190 schema:value 35031858
    191 rdf:type schema:PropertyValue
    192 N947d891043564b6d942609f92aad0f3c schema:name doi
    193 schema:value 10.1007/s00439-021-02416-7
    194 rdf:type schema:PropertyValue
    195 N9c811f1feeeb4ed5a792f4330f465f84 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    196 schema:name Phenotype
    197 rdf:type schema:DefinedTerm
    198 Na0e805df041b4066befba898d9687c93 rdf:first sg:person.01020376771.12
    199 rdf:rest rdf:nil
    200 Nbae992f5dabc4fc9883d85bbb90448ed rdf:first sg:person.01324346645.35
    201 rdf:rest Nc474d034334f4fb2b64edbd18b77a1b5
    202 Nc474d034334f4fb2b64edbd18b77a1b5 rdf:first sg:person.0661323161.22
    203 rdf:rest Na0e805df041b4066befba898d9687c93
    204 Ncb91d40a6a4f40809c316381942ac464 rdf:first sg:person.010027005677.62
    205 rdf:rest N710817e393c543cebde9520aee0b1aee
    206 Ncf2a23280c534632a23e9a0f7754da34 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    207 schema:name Mutant Proteins
    208 rdf:type schema:DefinedTerm
    209 Nd4b1dcaac47b4a5085eec26a320e9d2f rdf:first sg:person.0665566724.29
    210 rdf:rest N46fd106dfd8043b28922faca0277f599
    211 Nd9f72fcd3b494f178b3f34f50b3f7dd2 schema:volumeNumber 141
    212 rdf:type schema:PublicationVolume
    213 Ndd126bee709647b280da0b3419a184a4 rdf:first sg:person.0771632630.14
    214 rdf:rest N1d823fdbbefb448cb093402867c516dc
    215 Ndd76ce85f2de4bd2b95364b22c73c858 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    216 schema:name Drosophila melanogaster
    217 rdf:type schema:DefinedTerm
    218 Ne2709102147f40d1b350a6352b86c801 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    219 schema:name Humans
    220 rdf:type schema:DefinedTerm
    221 Nf0532e8d0de947b3b9384c4a01302e64 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    222 schema:name Mutation, Missense
    223 rdf:type schema:DefinedTerm
    224 Nf98f9ca1bd4a4712917580685020408a rdf:first sg:person.01112357030.87
    225 rdf:rest N150096af0de24f4492896f8e44548321
    226 Nfa5f8b1b5d35440d8f522c567bc7f00e rdf:first sg:person.01226075705.36
    227 rdf:rest Ncb91d40a6a4f40809c316381942ac464
    228 Nfe6af74b0a3b4df59d399b57fe0bc5e2 rdf:first sg:person.014500613032.37
    229 rdf:rest Nf98f9ca1bd4a4712917580685020408a
    230 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    231 schema:name Medical and Health Sciences
    232 rdf:type schema:DefinedTerm
    233 anzsrc-for:1109 schema:inDefinedTermSet anzsrc-for:
    234 schema:name Neurosciences
    235 rdf:type schema:DefinedTerm
    236 sg:grant.5557423 http://pending.schema.org/fundedItem sg:pub.10.1007/s00439-021-02416-7
    237 rdf:type schema:MonetaryGrant
    238 sg:grant.9198895 http://pending.schema.org/fundedItem sg:pub.10.1007/s00439-021-02416-7
    239 rdf:type schema:MonetaryGrant
    240 sg:grant.9207919 http://pending.schema.org/fundedItem sg:pub.10.1007/s00439-021-02416-7
    241 rdf:type schema:MonetaryGrant
    242 sg:grant.9208415 http://pending.schema.org/fundedItem sg:pub.10.1007/s00439-021-02416-7
    243 rdf:type schema:MonetaryGrant
    244 sg:grant.9208923 http://pending.schema.org/fundedItem sg:pub.10.1007/s00439-021-02416-7
    245 rdf:type schema:MonetaryGrant
    246 sg:journal.1085982 schema:issn 0340-6717
    247 1432-1203
    248 schema:name Human Genetics
    249 schema:publisher Springer Nature
    250 rdf:type schema:Periodical
    251 sg:person.010027005677.62 schema:affiliation grid-institutes:grid.41156.37
    252 schema:familyName Sun
    253 schema:givenName Jia-Hui
    254 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010027005677.62
    255 rdf:type schema:Person
    256 sg:person.01011242157.36 schema:affiliation grid-institutes:grid.414818.0
    257 schema:familyName Rinaldi
    258 schema:givenName Berardo
    259 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01011242157.36
    260 rdf:type schema:Person
    261 sg:person.01020376771.12 schema:affiliation grid-institutes:grid.268441.d
    262 schema:familyName Matsumoto
    263 schema:givenName Naomichi
    264 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01020376771.12
    265 rdf:type schema:Person
    266 sg:person.010452633515.16 schema:affiliation grid-institutes:grid.470126.6
    267 schema:familyName Tsuchida
    268 schema:givenName Naomi
    269 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010452633515.16
    270 rdf:type schema:Person
    271 sg:person.01112357030.87 schema:affiliation grid-institutes:grid.412181.f
    272 schema:familyName Tohyama
    273 schema:givenName Jun
    274 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01112357030.87
    275 rdf:type schema:Person
    276 sg:person.01152453333.59 schema:affiliation grid-institutes:grid.10825.3e
    277 schema:familyName Bayat
    278 schema:givenName Allan
    279 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01152453333.59
    280 rdf:type schema:Person
    281 sg:person.01161402433.96 schema:affiliation grid-institutes:grid.41156.37
    282 schema:familyName Shi
    283 schema:givenName Yun Stone
    284 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01161402433.96
    285 rdf:type schema:Person
    286 sg:person.01204506642.82 schema:affiliation grid-institutes:grid.412220.7
    287 schema:familyName Gerard
    288 schema:givenName Benedicte
    289 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01204506642.82
    290 rdf:type schema:Person
    291 sg:person.01213474560.37 schema:affiliation grid-institutes:grid.268441.d
    292 schema:familyName Mizuguchi
    293 schema:givenName Takeshi
    294 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01213474560.37
    295 rdf:type schema:Person
    296 sg:person.01226075705.36 schema:affiliation grid-institutes:grid.275033.0
    297 schema:familyName Miyoshi
    298 schema:givenName Keita
    299 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01226075705.36
    300 rdf:type schema:Person
    301 sg:person.01227034056.86 schema:affiliation grid-institutes:grid.470126.6
    302 schema:familyName Uchiyama
    303 schema:givenName Yuri
    304 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01227034056.86
    305 rdf:type schema:Person
    306 sg:person.013065235571.92 schema:affiliation grid-institutes:None
    307 schema:familyName Komatsubara
    308 schema:givenName Takao
    309 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013065235571.92
    310 rdf:type schema:Person
    311 sg:person.01324346645.35 schema:affiliation grid-institutes:grid.275033.0
    312 schema:familyName Saito
    313 schema:givenName Kuniaki
    314 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01324346645.35
    315 rdf:type schema:Person
    316 sg:person.014257250371.26 schema:affiliation grid-institutes:grid.268441.d
    317 schema:familyName Hamada
    318 schema:givenName Keisuke
    319 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014257250371.26
    320 rdf:type schema:Person
    321 sg:person.014500613032.37 schema:affiliation grid-institutes:grid.410714.7
    322 schema:familyName Kato
    323 schema:givenName Mitsuhiro
    324 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014500613032.37
    325 rdf:type schema:Person
    326 sg:person.0661323161.22 schema:affiliation grid-institutes:grid.470126.6
    327 schema:familyName Miyatake
    328 schema:givenName Satoko
    329 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0661323161.22
    330 rdf:type schema:Person
    331 sg:person.0665566724.29 schema:affiliation grid-institutes:grid.268441.d
    332 schema:familyName Fujita
    333 schema:givenName Atsushi
    334 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0665566724.29
    335 rdf:type schema:Person
    336 sg:person.0737306417.00 schema:affiliation grid-institutes:grid.268441.d
    337 schema:familyName Ogata
    338 schema:givenName Kazuhiro
    339 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0737306417.00
    340 rdf:type schema:Person
    341 sg:person.0771632630.14 schema:affiliation grid-institutes:grid.268441.d
    342 schema:familyName Saida
    343 schema:givenName Ken
    344 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0771632630.14
    345 rdf:type schema:Person
    346 sg:person.0777321437.45 schema:affiliation grid-institutes:grid.268441.d
    347 schema:familyName Hamanaka
    348 schema:givenName Kohei
    349 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0777321437.45
    350 rdf:type schema:Person
    351 sg:pub.10.1007/s00415-015-7984-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050069422
    352 https://doi.org/10.1007/s00415-015-7984-0
    353 rdf:type schema:CreativeWork
    354 sg:pub.10.1007/s11064-015-1749-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019509142
    355 https://doi.org/10.1007/s11064-015-1749-0
    356 rdf:type schema:CreativeWork
    357 sg:pub.10.1038/361031a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042608618
    358 https://doi.org/10.1038/361031a0
    359 rdf:type schema:CreativeWork
    360 sg:pub.10.1038/42009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042789897
    361 https://doi.org/10.1038/42009
    362 rdf:type schema:CreativeWork
    363 sg:pub.10.1038/cddis.2013.232 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031461285
    364 https://doi.org/10.1038/cddis.2013.232
    365 rdf:type schema:CreativeWork
    366 sg:pub.10.1038/gim.2015.30 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022229472
    367 https://doi.org/10.1038/gim.2015.30
    368 rdf:type schema:CreativeWork
    369 sg:pub.10.1038/jhg.2016.12 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016186613
    370 https://doi.org/10.1038/jhg.2016.12
    371 rdf:type schema:CreativeWork
    372 sg:pub.10.1038/nature23479 schema:sameAs https://app.dimensions.ai/details/publication/pub.1090859634
    373 https://doi.org/10.1038/nature23479
    374 rdf:type schema:CreativeWork
    375 sg:pub.10.1038/ncomms9018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029523624
    376 https://doi.org/10.1038/ncomms9018
    377 rdf:type schema:CreativeWork
    378 sg:pub.10.1038/ng.101 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001071534
    379 https://doi.org/10.1038/ng.101
    380 rdf:type schema:CreativeWork
    381 sg:pub.10.1038/nmeth0410-248 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007489634
    382 https://doi.org/10.1038/nmeth0410-248
    383 rdf:type schema:CreativeWork
    384 sg:pub.10.1038/nmeth0810-575 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028459136
    385 https://doi.org/10.1038/nmeth0810-575
    386 rdf:type schema:CreativeWork
    387 sg:pub.10.1038/nn.4589 schema:sameAs https://app.dimensions.ai/details/publication/pub.1086070786
    388 https://doi.org/10.1038/nn.4589
    389 rdf:type schema:CreativeWork
    390 sg:pub.10.1038/nprot.2009.86 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015642657
    391 https://doi.org/10.1038/nprot.2009.86
    392 rdf:type schema:CreativeWork
    393 sg:pub.10.1038/nrn.2016.37 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025635946
    394 https://doi.org/10.1038/nrn.2016.37
    395 rdf:type schema:CreativeWork
    396 sg:pub.10.1038/s10038-020-00853-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1131567574
    397 https://doi.org/10.1038/s10038-020-00853-2
    398 rdf:type schema:CreativeWork
    399 sg:pub.10.1038/s41586-020-2308-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1127885244
    400 https://doi.org/10.1038/s41586-020-2308-7
    401 rdf:type schema:CreativeWork
    402 sg:pub.10.1186/1750-1172-9-49 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032812490
    403 https://doi.org/10.1186/1750-1172-9-49
    404 rdf:type schema:CreativeWork
    405 sg:pub.10.1186/s13073-020-00725-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1125709453
    406 https://doi.org/10.1186/s13073-020-00725-6
    407 rdf:type schema:CreativeWork
    408 grid-institutes:None schema:alternateName Department of Child Neurology, NHO Nishiniigata Chuo Hospital, Niigata, Niigata, Japan
    409 schema:name Department of Child Neurology, NHO Nishiniigata Chuo Hospital, Niigata, Niigata, Japan
    410 rdf:type schema:Organization
    411 grid-institutes:grid.10825.3e schema:alternateName Institute for Regional Health Services Research, University of Southern Denmark, Odense, Denmark
    412 schema:name Department for Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark
    413 Institute for Regional Health Services Research, University of Southern Denmark, Odense, Denmark
    414 rdf:type schema:Organization
    415 grid-institutes:grid.268441.d schema:alternateName Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
    416 Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
    417 schema:name Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
    418 Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
    419 rdf:type schema:Organization
    420 grid-institutes:grid.275033.0 schema:alternateName Division of Invertebrate Genetics, Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan
    421 schema:name Division of Invertebrate Genetics, Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan
    422 Invertebrate Genetics Laboratory, Department of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan
    423 rdf:type schema:Organization
    424 grid-institutes:grid.410714.7 schema:alternateName Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan
    425 schema:name Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan
    426 rdf:type schema:Organization
    427 grid-institutes:grid.41156.37 schema:alternateName Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China
    428 schema:name Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School, Nanjing University, Nanjing, China
    429 rdf:type schema:Organization
    430 grid-institutes:grid.412181.f schema:alternateName Niigata University Medical and Dental Hospital, Niigata, Niigata, Japan
    431 schema:name Department of Child Neurology, NHO Nishiniigata Chuo Hospital, Niigata, Niigata, Japan
    432 Niigata University Medical and Dental Hospital, Niigata, Niigata, Japan
    433 rdf:type schema:Organization
    434 grid-institutes:grid.412220.7 schema:alternateName Laboratoires de Diagnostic Génétique, Institut Medical d’Alsace, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
    435 schema:name Laboratoires de Diagnostic Génétique, Institut Medical d’Alsace, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
    436 rdf:type schema:Organization
    437 grid-institutes:grid.414818.0 schema:alternateName Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
    438 schema:name Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
    439 rdf:type schema:Organization
    440 grid-institutes:grid.470126.6 schema:alternateName Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
    441 Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
    442 schema:name Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
    443 Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
    444 Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Kanagawa, Japan
    445 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...