A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia.
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 alpha1 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.
del Giudice
E M
EM
Department of Pediatrics, Second University of Naples, Naples, Italy.
Coppola
G
G
Bellini
G
G
Cirillo
G
G
Scuccimarra
G
G
Pascotto
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009422:Nervous System Diseases / Q000235:genetics*; D010375:Pedigree; D018009:Receptors, Glycine / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D008565:Membrane Proteins; D018009:Receptors, Glycine; D004247:DNA