Abstract
We investigated the molecular basis of hyperekplexia (STHE), an inherited neurological disorder characterised by neonatal hypertonia and an exaggerated startle response, in a kindred and identified a novel missense mutation in the pore-lining M2 domain of the α1 subunit of the glycine receptor (GLRA1). Sequencing analysis of all exons of the GLRA1 gene revealed a G1158A base transition in affected, heterozygous patients. The base transition results in a valine to methionine substitution at codon 260 in the middle of the M2 transmembrane domain. The location within the M2 domain suggests for this substitution a likely role in altering ion channel properties.
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Shiang R, Ryan SG, Zhu YZ, Hahn AF, O Connell P, Wasmuth JJ . Mutation in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia Nat Genet 1993 5: 351–358
Rees MI, Andrew M, Jawad S, Owen MJ . Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitor glycine receptor Hum Mol Genet 1994 3: 2175–2179
Langosh D, Thomas L, Betz H . Conserved quaternary structure of ligand-gated ion channels: the post-synaptic glycine receptor is a pentamer PNAS 1988 85: 7394–7398
Lynch JW, Rajendra S, Pierce KD, Handford CA, Barry PH, Schofield PR . Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel EMBO J 1997 16: 110–120
Rajendra S, Lynch JW, Pierce KD, French CR, Barry PH, Schofield PR . Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor JBC 1994 269: 18739–18742
Vigevano F, Di Capua M, Dalla Bernardina B . Startle disease: an avoidable cause of sudden infant death Lancet 1989 28: 216
Elmslie FV, Hutchings SM, Spencer V et al. Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis J Med Genet 1996 33: 435–436
Schofield PR . Genetics, an alternative way to discover, characterize and understand ion channels Clin Exp Pharmacol Physiol 2001 28: 84–88
Milani N, Dalprà L, del Prete A, Zanini R, Larizza L . A novel mutation (Gln 266His) in the alpha 1 subunit of the inhibitory glycine-receptor gene (GLRA1) in hereditary hyperekplexia Am J Hum Genet 1996 58: 420–422
Miller C . Genetic manipulation of ion channels: a new approach to structure and mechanism Neuron 1989 2: 1195–1205
Moorhouse AJ, Jacques P, Barry PH, Schofield PR . The startle disease mutation Q266H, in the second transmembrane domain of the human glycine receptor, impairs channel gating Mol Pharmacol 1999 55: 386–395
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del Giudice, E., Coppola, G., Bellini, G. et al. A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia. Eur J Hum Genet 9, 873–876 (2001). https://doi.org/10.1038/sj.ejhg.5200729
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DOI: https://doi.org/10.1038/sj.ejhg.5200729
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