Title
Hyperekplexia associated with compound heterozygote mutations in the <tex>$\beta$</tex>-subunit of the human inhibitory glycine receptor (**GLRB**) Hyperekplexia associated with compound heterozygote mutations in the <tex>$\beta$</tex>-subunit of the human inhibitory glycine receptor (**GLRB**)
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Oxford ,
Subject
Human medicine
Source (journal)
Human molecular genetics. - Oxford
Volume/pages
11(2002) :7 , p. 853-860
ISSN
0964-6906
ISI
000174797100014
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Hyperekplexia (MIM: 149400) is a neurological disorder characterized by an excessive startle response which can be caused by mutations in the α1-subunit (GLRA1) of the heteropentameric human inhibitory glycine receptor (hGlyR). These receptors facilitate fast-response, inhibitory glycinergic neurotransmission in the brainstem and spinal cord leading to a rapid modification and reduction of the excitatory startle response. Mutations in the β-subunit of GlyR (glrb) occur in a murine model of hyperekplexia (spastic), but have not been detected in human hyperekplexia. Following mutation analysis of the human β-subunit of hGlyR (GLRB) in a cohort of 22 hyperekplexia patients, we provide evidence to confirm that GLRB mutations can cause human hyperekplexia. A missense (G920A resulting in G229D) and a splice site mutation (IVS5+5G→A) occurred together in a compound heterozygote with a transient hyperekplexia phenotype. Exon trap analysis revealed that IVS5+5G→A results in the exclusion of exon 5 from GLRB transcripts. Electrophysiological studies showed reduced sensitivity to agonist mediated activation of the α1β (G229D) GlyR suggesting that GlyR β&#8208;subunits are not restricted to conferring modulatory influences and maintaining structural integrity, but may also play a functional role in hGlyR ligand binding.
E-info
https://repository.uantwerpen.be/docman/iruaauth/fe7110/f3b74d86f73.pdf
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