KEGG   DISEASE: Neurodevelopmental disorder with glutamatergic synapse dysfunction
Entry
H02705                      Disease                                
Name
Neurodevelopmental disorder with glutamatergic synapse dysfunction
  Subgroup
NED with language impairment and behavioral abnormalities (NEDLIB) [DS:H02887]
NED with or without seizures and gait abnormalities (NEDSGA) [DS:H02888]
NED with or without hyperkinetic movements and seizures (NDHMSD/NDHMSR) [DS:H02865]
NED with seizures, hypotonia, and brain abnormalities (NEDSHBA) [DS:H02886]
NED with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB)
NED with hypotonia and dysmorphic facies (NEDHYDF) [DS:H02885]
Description
Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS) and mediates its actions via activation of both ionotropic and metabotropic receptor families. Recent studies have shown that rare mutations in glutamate receptors and synaptic scaffold proteins are associated with neurodevelopmental disorders.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
 06 Mental, behavioural or neurodevelopmental disorders
  Neurodevelopmental disorders
   6A0Y  Other specified neurodevelopmental disorders
    H02705  Neurodevelopmental disorder with glutamatergic synapse dysfunction
Pathway
hsa04724 Glutamatergic synapse   
hsa04020  Calcium signaling pathway
Gene
(NEDLIB) GRIA2 [HSA:2891] [KO:K05198]
(NEDSGA) GRIA4 [HSA:2893] [KO:K05200]
(NDHMSD/NDHMSR) GRIN1 [HSA:2902] [KO:K05208]
(NEDSHBA) GRM7 [HSA:2917] [KO:K04609]
(NEDHISB) GNAI1 [HSA:2770] [KO:K04630]
(NEDHYDF) GNB2 [HSA:2783] [KO:K04537]
Other DBs
ICD-11: 6A0Y
OMIM: 619854
Reference
  Authors
Moretto E, Murru L, Martano G, Sassone J, Passafaro M
  Title
Glutamatergic synapses in neurodevelopmental disorders.
  Journal
Prog Neuropsychopharmacol Biol Psychiatry 84:328-342 (2018)
DOI:10.1016/j.pnpbp.2017.09.014
Reference
  Authors
Kew JN, Kemp JA
  Title
Ionotropic and metabotropic glutamate receptor structure and pharmacology.
  Journal
Psychopharmacology (Berl) 179:4-29 (2005)
DOI:10.1007/s00213-005-2200-z
Reference
PMID:31300657 (NEDLIB)
  Authors
Salpietro V, Dixon CL, Guo H, Bello OD, Vandrovcova J, Efthymiou S, Maroofian R, Heimer G, Burglen L, Valence S, Torti E, Hacke M, Rankin J, Tariq H, Colin E, Procaccio V, Striano P, Mankad K, Lieb A, Chen S, Pisani L, Bettencourt C, Mannikko R, Manole A, Brusco A, Grosso E, Ferrero GB, Armstrong-Moron J, Gueden S, Bar-Yosef O, Tzadok M, Monaghan KG, Santiago-Sim T, Person RE, Cho MT, Willaert R, Yoo Y, Chae JH, Quan Y, Wu H, Wang T, Bernier RA, Xia K, Blesson A, Jain M, Motazacker MM, Jaeger B, Schneider AL, Boysen K, Muir AM, Myers CT, Gavrilova RH, Gunderson L, Schultz-Rogers L, Klee EW, Dyment D, Osmond M, Parellada M, Llorente C, Gonzalez-Penas J, Carracedo A, Van Haeringen A, Ruivenkamp C, Nava C, Heron D, Nardello R, Iacomino M, Minetti C, Skabar A, Fabretto A, Raspall-Chaure M, Chez M, Tsai A, Fassi E, Shinawi M, Constantino JN, De Zorzi R, Fortuna S, Kok F, Keren B, Bonneau D, Choi M, Benzeev B, Zara F, Mefford HC, Scheffer IE, Clayton-Smith J, Macaya A, Rothman JE, Eichler EE, Kullmann DM, Houlden H
  Title
AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.
  Journal
Nat Commun 10:3094 (2019)
DOI:10.1038/s41467-019-10910-w
Reference
PMID:29220673 (NEDSGA)
  Authors
Martin S, Chamberlin A, Shinde DN, Hempel M, Strom TM, Schreiber A, Johannsen J, Ousager LB, Larsen MJ, Hansen LK, Fatemi A, Cohen JS, Lemke J, Sorensen KP, Helbig KL, Lessel D, Abou Jamra R
  Title
De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities.
  Journal
Am J Hum Genet 101:1013-1020 (2017)
DOI:10.1016/j.ajhg.2017.11.004
Reference
PMID:28228639 (NDHMSD)
  Authors
Chen W, Shieh C, Swanger SA, Tankovic A, Au M, McGuire M, Tagliati M, Graham JM, Madan-Khetarpal S, Traynelis SF, Yuan H, Pierson TM
  Title
GRIN1 mutation associated with intellectual disability alters NMDA receptor trafficking and function.
  Journal
J Hum Genet 62:589-597 (2017)
DOI:10.1038/jhg.2017.19
Reference
PMID:27164704 (NDHMSR)
  Authors
Lemke JR, Geider K, Helbig KL, Heyne HO, Schutz H, Hentschel J, Courage C, Depienne C, Nava C, Heron D, Moller RS, Hjalgrim H, Lal D, Neubauer BA, Nurnberg P, Thiele H, Kurlemann G, Arnold GL, Bhambhani V, Bartholdi D, Pedurupillay CR, Misceo D, Frengen E, Stromme P, Dlugos DJ, Doherty ES, Bijlsma EK, Ruivenkamp CA, Hoffer MJ, Goldstein A, Rajan DS, Narayanan V, Ramsey K, Belnap N, Schrauwen I, Richholt R, Koeleman BP, Sa J, Mendonca C, de Kovel CG, Weckhuysen S, Hardies K, De Jonghe P, De Meirleir L, Milh M, Badens C, Lebrun M, Busa T, Francannet C, Piton A, Riesch E, Biskup S, Vogt H, Dorn T, Helbig I, Michaud JL, Laube B, Syrbe S
  Title
Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy.
  Journal
Neurology 86:2171-8 (2016)
DOI:10.1212/WNL.0000000000002740
Reference
PMID:33500274 (NEDSHBA)
  Authors
Song JM, Kang M, Park DH, Park S, Lee S, Suh YH
  Title
Pathogenic GRM7 Mutations Associated with Neurodevelopmental Disorders Impair Axon Outgrowth and Presynaptic Terminal Development.
  Journal
J Neurosci 41:2344-2359 (2021)
DOI:10.1523/JNEUROSCI.2108-20.2021
Reference
PMID:33473207 (NEDHISB)
  Authors
Muir AM, Gardner JF, van Jaarsveld RH, de Lange IM, van der Smagt JJ, Wilson GN, Dubbs H, Goldberg EM, Zitano L, Bupp C, Martinez J, Srour M, Accogli A, Alhakeem A, Meltzer M, Gropman A, Brewer C, Caswell RC, Montgomery T, McKenna C, McKee S, Powell C, Vasudevan PC, Brady AF, Joss S, Tysoe C, Noh G, Tarnopolsky M, Brady L, Zafar M, Schrier Vergano SA, Murray B, Sawyer L, Hainline BE, Sapp K, DeMarzo D, Huismann DJ, Wentzensen IM, Schnur RE, Monaghan KG, Juusola J, Rhodes L, Dobyns WB, Lecoquierre F, Goldenberg A, Polster T, Axer-Schaefer S, Platzer K, Klockner C, Hoffman TL, MacArthur DG, O'Leary MC, VanNoy GE, England E, Varghese VC, Mefford HC
  Title
Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.
  Journal
Genet Med 23:881-887 (2021)
DOI:10.1038/s41436-020-01076-8
Reference
PMID:31698099 (NEDHYDF)
  Authors
Fukuda T, Hiraide T, Yamoto K, Nakashima M, Kawai T, Yanagi K, Ogata T, Saitsu H
  Title
Exome reports A de novo GNB2 variant associated with global developmental delay, intellectual disability, and dysmorphic features.
  Journal
Eur J Med Genet 63:103804 (2020)
DOI:10.1016/j.ejmg.2019.103804
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