دورية أكاديمية
Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes.
| العنوان: | Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. |
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| المؤلفون: | 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, Kutsche, Kerstin |
| المصدر: | Nature Genetics, 42 (11), 1021-6 (2010) |
| بيانات النشر: | Nature Publishing Group, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | 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, Life sciences, Genetics & genetic processes, Sciences du vivant, Génétique & processus génétiques |
| الوصف: | 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. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501Test article |
| اللغة: | English |
| العلاقة: | urn:issn:1061-4036; urn:issn:1546-1718 |
| DOI: | 10.1038/ng.677 |
| الوصول الحر: | https://orbi.uliege.be/handle/2268/82730Test |
| حقوق: | restricted access http://purl.org/coar/access_right/c_16ecTest info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsorb.82730 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.1038/ng.677 |
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