title: A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype.
abstract: Hyperekplexia (MIM #149400) is a rare neurological disorder characterized by an exaggerated startle response, infantile hypertonia and hyperreflexia without spasticity, a hesitant gait that usually improves by 3 years of age, and nocturnal myoclonus. Familial hyperekplexia is usually autosomal dominant resulting from mutations in the inhibitory glycine receptor subunit alpha 1 (GLRA1) gene on chromosome 5q. We identified a 3-generation family with progressively severe phenotypes of hyperekplexia. All affected family members were found to be heterozygous for a novel arginine271proline mutation in GLRA1. Long-term follow-up of the affected members of the third generation, now aged 6 and 7 years, reveals enhanced startle responses and persistent hypertonia of the extremities without clonus or a catch, tight heel cords and abnormal toe-walking gait, and plantar flexor reflexes. The 7-year-old child recently reponded well to a benzodiazepine. Future studies are warranted to examine whether this new missense mutation is solely responsible for this atypical phenotype.
authors.affiliation: J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Gregory
authors.forename: Greg F
authors.initials: GF
authors.lastname: Guzauskas
authors.forename: Terence S
authors.initials: TS
authors.lastname: Edgar
authors.forename: Kate B
authors.initials: KB
authors.lastname: Clarkson
authors.forename: Anand K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Kenton R
authors.initials: KR
authors.lastname: Holden
mesh_terms: D000328:Adult; D001741:Black or African American; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009122:Muscle Hypertonia / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D011392:Proline / Q000235:genetics; D018009:Receptors, Glycine / Q000235:genetics*; D012021:Reflex, Abnormal / Q000235:genetics* / Q000502:physiology
chemical_list: C000657604:GLRA1 protein, human; D018009:Receptors, Glycine; D001120:Arginine; D011392:Proline