title: Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor.
abstract: Startle disease, or hyperekplexia, is characterized by an exaggerated startle reflex and neonatal hypertonia. An autosomal dominant form of the disorder is associated with mutations in the same codon of the alpha 1 subunit of the inhibitory glycine receptor (GLRA 1) resulting in the substitution of an uncharged amino acid for Arg271 in the mature protein. However, recessive transmission is seen in the mouse mutant spasmodic which resembles startle disease phenotypically and is also associated with mutations in Glra 1. We have confirmed the finding of Arg271 mutations in individuals with startle disease in a UK family showing autosomal dominant transmission. In addition we describe an apparently sporadic case, the offspring of a consanguineous mating, who is homozygous for a novel mutation (T1112A) in GLRA 1, which results in the substitution of asparagine for isoleucine at position 244 of the mature protein. This suggests that human startle disease can display recessive as well as dominant inheritance resulting from different mutations in GLRA 1.
authors.affiliation: Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: M I
authors.initials: MI
authors.lastname: Rees
authors.forename: M
authors.initials: M
authors.lastname: Andrew
authors.forename: S
authors.initials: S
authors.lastname: Jawad
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009127:Muscle Rigidity / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000235:genetics*; D012021:Reflex, Abnormal / Q000235:genetics*
chemical_list: D018009:Receptors, Glycine