title: The impact of human hyperekplexia mutations on glycine receptor structure and function.
abstract: Hyperekplexia is a rare neurological disorder characterized by neonatal hypertonia, exaggerated startle responses to unexpected stimuli and a variable incidence of apnoea, intellectual disability and delays in speech acquisition. The majority of motor defects are successfully treated by clonazepam. Hyperekplexia is caused by hereditary mutations that disrupt the functioning of inhibitory glycinergic synapses in neuromotor pathways of the spinal cord and brainstem. The human glycine receptor α1 and β subunits, which predominate at these synapses, are the major targets of mutations. International genetic screening programs, that together have analysed several hundred probands, have recently generated a clear picture of genotype-phenotype correlations and the prevalence of different categories of hyperekplexia mutations. Focusing largely on this new information, this review seeks to summarise the effects of mutations on glycine receptor structure and function and how these functional alterations lead to hyperekplexia.
authors.forename: Anna
authors.initials: A
authors.lastname: Bode
authors.affiliation: Queensland Brain Institute and School of Biomedical Sciences, The University of Queensland, Queensland 4072, Australia. j.lynch@uq.edu.au.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Lynch
mesh_terms: D006801:Humans; D015640:Ion Channel Gating; D009154:Mutation / Q000235:genetics*; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018009:Receptors, Glycine / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016750:Stiff-Person Syndrome / Q000235:genetics* / Q000503:physiopathology
chemical_list: D021122:Protein Subunits; D018009:Receptors, Glycine