title: A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia.
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 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.
authors.affiliation: Department of Pediatrics, Second University of Naples, Naples, Italy.
authors.forename: E M
authors.initials: EM
authors.lastname: del Giudice
authors.forename: G
authors.initials: G
authors.lastname: Coppola
authors.forename: G
authors.initials: G
authors.lastname: Bellini
authors.forename: G
authors.initials: G
authors.lastname: Cirillo
authors.forename: G
authors.initials: G
authors.lastname: Scuccimarra
authors.forename: A
authors.initials: A
authors.lastname: Pascotto
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; D018009:Receptors, Glycine; D004247:DNA