The novel hyperekplexia allele GLRA1(S267N) affects the ethanol site of the glycine receptor.
Mutations in the GLRA1 gene, which encodes the alpha1-subunit of the inhibitory glycine receptor (GlyR), are the underlying causes in the majority of cases of hereditary startle disease (OMIM no. 149400). GlyRs are modulated by alcohols and volatile anesthetics, where a specific amino acid at position 267 has been implicated in receptor modulation. We describe a hyperekplexia family carrying the novel dominant missense allele GLRA1(S267N), that affects agonist responses and ethanol modulation of the mutant receptor. This study implies that a disease-related receptor allele carries the potential to alter drug responses in affected patients.
Becker
Kristina
K
Institut für Biochemie, Emil Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany.
Breitinger
Hans-Georg
HG
Humeny
Andreas
A
Meinck
Hans-Michael
HM
Dietz
Bernd
B
Aksu
Fuat
F
Becker
Cord-Michael
CM
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D018009:Receptors, Glycine / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D012021:Reflex, Abnormal / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics*; D016750:Stiff-Person Syndrome / Q000235:genetics* / Q000378:metabolism
C000657604:GLRA1 protein, human; D018009:Receptors, Glycine; D000431:Ethanol