Episodic ataxia associated with EAAT1 mutation C186S affecting glutamate reuptake
| Autor: | Bruce D. Howard, Elles M. J. Boon, Hafsa Mamsa, Stef L. M. Bakker, Rune R. Frants, Anine H. Stam, Michel D. Ferrari, Arn M. J. M. van den Maagdenberg, Boukje de Vries, Robert W. Baloh, Gisela M. Terwindt, Kaate R J Vanmolkot, Joost Haan, Joanna C. Jen, Jijun Wan |
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| Přispěvatelé: | Human genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Genetic Markers Male medicine.medical_specialty Genotype Migraine Disorders DNA Mutational Analysis Mutant Inheritance Patterns Glutamic Acid Hemiplegia Biology medicine.disease_cause Arts and Humanities (miscellaneous) Seizures Cerebellum Internal medicine medicine Humans Missense mutation Glutamate reuptake Genetic Predisposition to Disease Genetic Testing Spinocerebellar Degenerations Brain Chemistry Episodic ataxia Genetics Mutation Glutamate receptor Middle Aged medicine.disease Pedigree Excitatory Amino Acid Transporter 1 Phenotype Endocrinology Migraine Female Neurology (clinical) Alternating hemiplegia |
| Zdroj: | Archives of Neurology, 66(1), 97-101. American Medical Association De Vries, B, Mamsa, H, Stam, A H, Wan, J, Bakker, S L M, Vanmolkot, K R J, Haan, J, Terwindt, G M, Boon, E M J, Howard, B D, Frants, R R, Baloh, R W, Ferrari, M D, Jen, J C & Van Den Maagdenberg, A M J M 2009, ' Episodic ataxia associated with EAAT1 mutation C186S affecting glutamate reuptake ', Archives of Neurology, vol. 66, no. 1, pp. 97-101 . https://doi.org/10.1001/archneurol.2008.535 |
| ISSN: | 0003-9942 |
| DOI: | 10.1001/archneurol.2008.535 |
| Popis: | Background Episodic ataxia (EA) is variably associated with additional neurologic symptoms. At least 4 genes have been implicated. Recently, a mutation in the SLC1A3 gene encoding the glutamate transporter EAAT1 was identified in a patient with severe episodic and progressive ataxia, seizures, alternating hemiplegia, and migraine headache. The mutant EAAT1 showed severely reduced uptake of glutamate. The syndrome was designated EA6 and shares overlapping clinical features with EA2, which is caused by mutations in CACNA1A . Objective To test the role of the SLC1A3 gene in EA. Design Genetic and functional studies. We analyzed the coding region of the SLC1A3 gene by direct sequencing. Setting Academic research. Patients DNA samples from 20 patients with EA (with or without interictal nystagmus) negative for CACNA1A mutations were analyzed. Main Outcome Measures We identified 1 novel EAAT1 mutation in a family with EA and studied the functional consequences of this mutation using glutamate uptake assay. Results We identified a missense C186S mutation that segregated with EA in 3 family members. The mutant EAAT1 showed a modest but significant reduction of glutamate uptake. Conclusions We broadened the clinical spectrum associated with SLC1A3 mutations to include milder manifestations of EA without seizures or alternating hemiplegia. The severity of EA6 symptoms appears to be correlated with the extent of glutamate transporter dysfunction. |
| Databáze: | OpenAIRE |
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