Journal article
Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease
Nature Genetics, Vol.38(7), pp.801-806
2006
Abstract
Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) α1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic cases, with mutations affecting other postsynaptic glycinergic proteins including the GlyR β subunit (GLRB), gephyrin (GPHN) and RhoGEF collybistin (ARHGEF9). However, many individuals diagnosed with sporadic hyperekplexia do not carry mutations in these genes. Here we show that missense, nonsense and frameshift mutations in SLC6A5 (ref. 8), encoding the presynaptic glycine transporter 2 (GlyT2), also cause hyperekplexia. Individuals with mutations in SLC6A5 present with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. SLC6A5 mutations result in defective subcellular GlyT2 localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na+ binding sites. © 2006 Nature Publishing Group.
Details
- Title
- Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease
- Authors
- M I Rees (Author) - University of Wales, United KingdomK Harvey (Author) - University College London, United KingdomB R Pearce (Author) - University College London, United KingdomS K Chung (Author) - University of Wales, United KingdomI C Duguid (Author) - University College London, United KingdomP Thomas (Author) - University College London, United KingdomS Beatty (Author) - University of Auckland, New ZealandG E Graham (Author) - Children's Hospital of Eastern Ontario, CanadaL Armstrong (Author) - Children's and Women's Health Centre of British Columbia, CanadaR Shiang (Author) - Virginia Commonwealth University Medical Center, United StatesK J Abbott (Author) - Adelaide Women's and Children's HospitalS M Zuberi (Author) - Royal Hospital for Sick Children, United KingdomJ B P Stephenson (Author) - Royal Hospital for Sick Children, United KingdomM J Owen (Author) - University of Wales College of Medicine, United KingdomM A J Tijssen (Author) - University of Amsterdam, NetherlandsA M J M Van Den Maagdenberg (Author) - Leiden University Medical Centre, NetherlandsT G Smart (Author) - University College London, United KingdomS Supplisson (Author) - Laboratoire de Neurobiologie, FranceRobert J Harvey (Author) - University College London, United Kingdom
- Publication details
- Nature Genetics, Vol.38(7), pp.801-806
- Publisher
- Nature Publishing Group
- Date published
- 2006
- DOI
- 10.1038/ng1814
- ISSN
- 1061-4036
- Copyright note
- Copyright © 2006 Nature Publishing Group. The accepted version is reproduced here in accordance with the publishers copyright policy. The definitive version is available from http://www.nature.com/ng/
- 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
- 99451192002621
- Output Type
- Journal article
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