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rdf:type |
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lifeskim:mentions |
umls-concept:C0026882,
umls-concept:C0031437,
umls-concept:C0080093,
umls-concept:C0220905,
umls-concept:C0439828,
umls-concept:C0679058,
umls-concept:C1415299,
umls-concept:C1415300,
umls-concept:C1524003,
umls-concept:C1547699,
umls-concept:C1711351,
umls-concept:C2700640
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pubmed:issue |
11
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pubmed:dateCreated |
2010-10-28
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pubmed:abstractText |
N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission in the mammalian brain. Two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits each form highly Ca²(+)-permeable cation channels which are blocked by extracellular Mg²(+) in a voltage-dependent manner. Either GRIN2B or GRIN2A, encoding the NMDA receptor subunits NR2B and NR2A, was found to be disrupted by chromosome translocation breakpoints in individuals with mental retardation and/or epilepsy. Sequencing of GRIN2B in 468 individuals with mental retardation revealed four de novo mutations: a frameshift, a missense and two splice-site mutations. In another cohort of 127 individuals with idiopathic epilepsy and/or mental retardation, we discovered a GRIN2A nonsense mutation in a three-generation family. In a girl with early-onset epileptic encephalopathy, we identified the de novo GRIN2A mutation c.1845C>A predicting the amino acid substitution p.N615K. Analysis of NR1-NR2A(N615K) (NR2A subunit with the p.N615K alteration) receptor currents revealed a loss of the Mg²(+) block and a decrease in Ca²(+) permeability. Our findings suggest that disturbances in the neuronal electrophysiological balance during development result in variable neurological phenotypes depending on which NR2 subunit of NMDA receptors is affected.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1546-1718
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pubmed:author |
pubmed-author:EndeleSabineS,
pubmed-author:FritschAngelaA,
pubmed-author:GeiderKirstenK,
pubmed-author:HellenbroichYorckY,
pubmed-author:KalscheuerVera MVM,
pubmed-author:KohlhaseJürgenJ,
pubmed-author:KortümFannyF,
pubmed-author:KutscheKerstinK,
pubmed-author:LaubeBodoB,
pubmed-author:MilhMathieuM,
pubmed-author:PientkaFriederike KFK,
pubmed-author:PoppBerntB,
pubmed-author:RappoldGudrunG,
pubmed-author:RauchAnitaA,
pubmed-author:ReisAndréA,
pubmed-author:RopersHans-HilgerHH,
pubmed-author:RosenbergerGeorgG,
pubmed-author:StefanovaIrinaI,
pubmed-author:TönniesHolgerH,
pubmed-author:TamerCeyhunC,
pubmed-author:UteMoogM,
pubmed-author:Van MaldergemLionelL,
pubmed-author:VillardLaurentL,
pubmed-author:VilleneuveNathalieN,
pubmed-author:WieczorekDagmarD,
pubmed-author:ZabelBernhardB,
pubmed-author:ZenkerMartinM,
pubmed-author:von SpiczakSarahS
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pubmed:issnType |
Electronic
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1021-6
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:20890276-Adolescent,
pubmed-meshheading:20890276-Adult,
pubmed-meshheading:20890276-Amino Acid Substitution,
pubmed-meshheading:20890276-Calcium,
pubmed-meshheading:20890276-Child,
pubmed-meshheading:20890276-Child, Preschool,
pubmed-meshheading:20890276-Epilepsy,
pubmed-meshheading:20890276-Female,
pubmed-meshheading:20890276-Humans,
pubmed-meshheading:20890276-Intellectual Disability,
pubmed-meshheading:20890276-Magnesium,
pubmed-meshheading:20890276-Male,
pubmed-meshheading:20890276-Mutation,
pubmed-meshheading:20890276-Nervous System Diseases,
pubmed-meshheading:20890276-Pedigree,
pubmed-meshheading:20890276-Polymorphism, Single Nucleotide,
pubmed-meshheading:20890276-Protein Subunits,
pubmed-meshheading:20890276-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:20890276-Transcription, Genetic
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pubmed:year |
2010
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pubmed:articleTitle |
Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes.
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pubmed:affiliation |
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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