Harvey, RJ;
Carta, E;
Pearce, BR;
Chung, SK;
Supplisson, S;
Rees, MI;
Harvey, K;
(2008)
A critical role for glycine transporters in hyperexcitability disorders.
Front Mol Neurosci
, 1
, Article 1. 10.3389/neuro.02.001.2008.
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Abstract
Defects in mammalian glycinergic neurotransmission result in a complex motor disorder characterized by neonatal hypertonia and an exaggerated startle reflex, known as hyperekplexia (OMIM 149400). This affects newborn children and is characterized by noise or touch-induced seizures that result in muscle stiffness and breath-holding episodes. Although rare, this disorder can have serious consequences, including brain damage and/or sudden infant death. The primary cause of hyperekplexia is missense and non-sense mutations in the glycine receptor (GlyR) alpha1 subunit gene (GLRA1) on chromosome 5q33.1, although we have also discovered rare mutations in the genes encoding the GlyR beta subunit (GLRB) and the GlyR clustering proteins gephyrin (GPNH) and collybistin (ARHGEF9). Recent studies of the Na(+)/Cl(-)-dependent glycine transporters GlyT1 and GlyT2 using mouse knockout models and human genetics have revealed that mutations in GlyT2 are a second major cause of hyperekplexia, while the phenotype of the GlyT1 knockout mouse resembles a devastating neurological disorder known as glycine encephalopathy (OMIM 605899). These findings highlight the importance of these transporters in regulating the levels of synaptic glycine.
Type: | Article |
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Title: | A critical role for glycine transporters in hyperexcitability disorders. |
Location: | Switzerland |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.3389/neuro.02.001.2008 |
Publisher version: | http://dx.doi.org/10.3389/neuro.02.001.2008 |
Language: | English |
Additional information: | PMCID: PMC2526004. © 2008 Harvey, Carta, Pearce, Chung, Supplisson, Rees and Harvey. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation. This document is protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission |
Keywords: | glycine transporters, GlyT1, GlyT2, VIAAT, hyperekplexia, startle disease, glycine encephalopathy |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
URI: | https://discovery.ucl.ac.uk/id/eprint/1350551 |
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