The genetics of hyperekplexia: more than startle!
Hyperekplexia is characterised by neonatal hypertonia and an exaggerated startle reflex in response to acoustic or tactile stimuli. Genetic analysis of this disorder has revealed mutations in genes for several postsynaptic proteins involved in glycinergic neurotransmission, including the glycine receptor (GlyR) alpha1 and beta subunits, gephyrin and collybistin. However, new research suggests that mutations in the gene encoding the presynaptic glycine transporter GlyT2 are a second major cause of human hyperekplexia, as well as congenital muscular dystonia type 2 (CMD2) in cattle. These findings raise the intriguing possibility that both presynaptic and postsynaptic causes of disease might also exist in related disorders, such as idiopathic generalised epilepsies, where mutations in inhibitory GABA(A) receptor subunit genes have already been identified.
Harvey
Robert J
RJ
Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, UK. robert.harvey@pharmacy.ac.uk
Topf
Maya
M
Harvey
Kirsten
K
Rees
Mark I
MI
D000818:Animals; D005820:Genetic Testing; D005998:Glycine / Q000378:metabolism; D006262:Health; D006801:Humans; D009122:Muscle Hypertonia / Q000235:genetics*; D018009:Receptors, Glycine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013216:Reflex, Startle / Q000235:genetics*; D013569:Synapses / Q000378:metabolism
D018009:Receptors, Glycine; D005998:Glycine