Journal article
The glycinergic system in human startle disease: A genetic screening approach
Frontiers in Molecular Neuroscience, Vol.3, 8
2010
Abstract
Human startle disease, also known as hyperekplexia (OMIM 149400), is a paroxysmal neurological disorder caused by defects in glycinergic neurotransmission. Hyperekplexia is characterised by an exaggerated startle reflex in response to tactile or acoustic stimuli which first presents as neonatal hypertonia, followed in some with episodes of life-threatening infantile apnoea. Genetic screening studies have demonstrated that hyperekplexia is genetically heterogeneous with several missense and nonsense mutations in the postsynaptic glycine receptor (GlyR) α1 subunit gene (GLRA1) as the primary cause. More recently, missense, nonsense and frameshift mutations have also been identified in the glycine transporter GlyT2 gene, SLC6A5, demonstrating a presynaptic component to this disease. Further mutations, albeit rare, have been identified in the genes encoding the GlyR β subunit (GLRB), collybistin (ARHGEF9) and gephyrin (GPHN)-all of which are postsynaptic proteins involved in orchestrating glycinergic neurotransmission. In this review, we describe the clinical ascertainment aspects, phenotypic considerations and the downstream molecular genetic tools utilised to analyse both presynaptic and postsynaptic components of this heterogeneous human neurological disorder. Moreover, we will describe how the ancient startle response is the preserve of glycinergic neurotransmission and how animal models and human hyperekplexia patients have provided synergistic evidence that implicates this inhibitory system in the control of startle reflexes. © 2010 Davies, Chung, Thomas, Robinson, Hammond, Mullins, Carta, Pearce, Harvey, Harvey and Rees.
Details
- Title
- The glycinergic system in human startle disease: A genetic screening approach
- Authors
- J S Davies (Author) - Swansea University, United KingdomS K Chung (Author) - Swansea University, United KingdomR H Thomas (Author) - Swansea University, United KingdomA Robinson (Author) - Swansea University, United KingdomC L Hammond (Author) - Swansea University, United KingdomJ G L Mullins (Author) - Swansea University, United KingdomE Carta (Author) - University College London, United KingdomB R Pearce (Author) - University College London, United KingdomK Harvey (Author) - University College London, United KingdomRobert J Harvey (Author) - University College London, United KingdomM I Rees (Author) - Swansea University, United Kingdom
- Publication details
- Frontiers in Molecular Neuroscience, Vol.3, 8; 10
- Publisher
- Frontiers Research Foundation
- Date published
- 2010
- DOI
- 10.3389/fnmol.2010.00008
- ISSN
- 1662-5099
- Copyright note
- Copyright © 2010 Davies, Chung, Thomas, Robinson, Hammond, Mullins, Carta, Pearce, Harvey, Harvey and Rees. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source re credited.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99450605902621
- Output Type
- Journal article
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