title: Novel mutation of GLRA1 in Omani families with hyperekplexia and mild mental retardation.
abstract: Hyperekplexia is characterized by neonatal hypertonia and exaggerated startle reflex in response to loud noise or tactile stimuli. Mutations in patients with hyperekplexia were evident in several genes encoding proteins involved in glycinergic neurotransmission, i.e., glycine receptor α and β subunits, collybistin, gephyrin, and glycine transporter 2. We clinically and genetically characterized two large, unrelated consanguineous families with hyperekplexia. Affected members of the two families manifested hyperekplexia with mild mental retardation. Patients exhibited a novel homozygote c.593G>C missense mutation in GLRA1, resulting in amino acid substitution p.W170S in the corresponding mature glycine receptor α1 subunit. This mutation was absent in 400 randomly selected chromosomes in the same population. In conclusion, a novel p.W170S mutation in the extracellular ligand binding domain of glycine receptor α1 subunit was detected in patients with hyperekplexia and mild mental retardation.
authors.affiliation: Department of Child Health, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman.
authors.forename: Amna Mohammed
authors.initials: AM
authors.lastname: Al-Futaisi
authors.forename: Mohammed Nasser
authors.initials: MN
authors.lastname: Al-Kindi
authors.forename: Al-Mundher
authors.initials: AM
authors.lastname: Al-Mawali
authors.forename: Roshan Lal
authors.initials: RL
authors.lastname: Koul
authors.forename: Samir
authors.initials: S
authors.lastname: Al-Adawi
authors.forename: Said Ali
authors.initials: SA
authors.lastname: Al-Yahyaee
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009122:Muscle Hypertonia / Q000235:genetics*; D020125:Mutation, Missense; D009850:Oman; D010375:Pedigree; D018009:Receptors, Glycine / Q000235:genetics*; D012021:Reflex, Abnormal / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics*
chemical_list: C000657604:GLRA1 protein, human; D018009:Receptors, Glycine