Reference : Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause v...
Scientific journals : Article
Life sciences : Genetics & genetic processes
http://hdl.handle.net/2268/82730
Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes.
English
Endele, Sabine [> > > >]
Rosenberger, Georg [> > > >]
Geider, Kirsten [> > > >]
Popp, Bernt [> > > >]
Tamer, Ceyhun [> > > >]
Stefanova, Irina [> > > >]
Milh, Mathieu [> > > >]
Kortum, Fanny [> > > >]
Fritsch, Angela [> > > >]
Pientka, Friederike K [> > > >]
Hellenbroich, Yorck [> > > >]
Kalscheuer, Vera M [> > > >]
Kohlhase, Jurgen [> > > >]
Moog, Ute [> > > >]
Rappold, Gudrun [> > > >]
Rauch, Anita [> > > >]
Ropers, Hans*-Hilger [> > > >]
von Spiczak, Sarah [> > > >]
Tonnies, Holger [> > > >]
Villeneuve, Nathalie [> > > >]
Villard, Laurent [> > > >]
Zabel, Bernhard [> > > >]
Zenker, Martin [> > > >]
Laube, Bodo [> > > >]
Reis, Andre [> > > >]
Wieczorek, Dagmar [> > > >]
Van Maldergem, Lionel [Centre Hospitalier Universitaire de Liège - CHU > > Génétique >]
Kutsche, Kerstin [> > > >]
2010
Nature Genetics
Nature Publishing Group
42
11
1021-6
Yes (verified by ORBi)
International
1061-4036
1546-1718
New York
NY
[en] Adolescent ; Adult ; Amino Acid Substitution ; Calcium/metabolism ; Child ; Child, Preschool ; Epilepsy/genetics ; Female ; Humans ; Magnesium/metabolism ; Male ; Mental Retardation/genetics ; Mutation ; Nervous System Diseases/genetics ; Pedigree ; Polymorphism, Single Nucleotide ; Protein Subunits/genetics ; Receptors, N-Methyl-D-Aspartate/genetics ; Transcription, Genetic
[en] 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 Ca(2)(+)-permeable cation channels which are blocked by extracellular Mg(2)(+) 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 Mg(2)(+) block and a decrease in Ca(2)(+) 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.
http://hdl.handle.net/2268/82730
10.1038/ng.677

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
Mutations in GRIN2A-5Van Maldergem.pdfPublisher postprint1.03 MBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.