A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype

Mary L Gregory, Greg F. Guzauskas, Terence S. Edgar, Kate B. Clarkson, Anand K. Srivastava, Kenton R. Holden

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1433-1438
Number of pages6
JournalJournal of Child Neurology
Volume23
Issue number12
DOIs
StatePublished - Dec 24 2008
Externally publishedYes

Fingerprint

Startle Reflex
Glycine Receptors
Gait
Muscle Hypertonia
Stiff-Person Syndrome
Phenotype
Abnormal Reflexes
Mutation
Myoclonus
Heel
Toes
Missense Mutation
Nervous System Diseases
Benzodiazepines
Walking
Reflex
Extremities
Chromosomes
Genes
Hyperekplexia

Keywords

  • Gene mutation
  • GLRA1
  • Hyperekplexia
  • Neurodevelopment
  • Startle
  • Stiff-boy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Gregory, M. L., Guzauskas, G. F., Edgar, T. S., Clarkson, K. B., Srivastava, A. K., & Holden, K. R. (2008). A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype. Journal of Child Neurology, 23(12), 1433-1438. https://doi.org/10.1177/0883073808320754

A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype. / Gregory, Mary L; Guzauskas, Greg F.; Edgar, Terence S.; Clarkson, Kate B.; Srivastava, Anand K.; Holden, Kenton R.

In: Journal of Child Neurology, Vol. 23, No. 12, 24.12.2008, p. 1433-1438.

Research output: Contribution to journalArticle

Gregory, ML, Guzauskas, GF, Edgar, TS, Clarkson, KB, Srivastava, AK & Holden, KR 2008, 'A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype', Journal of Child Neurology, vol. 23, no. 12, pp. 1433-1438. https://doi.org/10.1177/0883073808320754
Gregory ML, Guzauskas GF, Edgar TS, Clarkson KB, Srivastava AK, Holden KR. A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype. Journal of Child Neurology. 2008 Dec 24;23(12):1433-1438. https://doi.org/10.1177/0883073808320754
Gregory, Mary L ; Guzauskas, Greg F. ; Edgar, Terence S. ; Clarkson, Kate B. ; Srivastava, Anand K. ; Holden, Kenton R. / A novel GLRA1 mutation associated with an atypical hyperekplexia phenotype. In: Journal of Child Neurology. 2008 ; Vol. 23, No. 12. pp. 1433-1438.
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