Polymorphisms in the glutamate transporter gene EAAT2 in European ALS patients
| Autor: | G Steers, Karen E. Morrison, Mandy Jackson, P N Leigh |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Genetics
Polymorphism Genetic Base Sequence Point mutation Amyotrophic Lateral Sclerosis Glutamate receptor Neurotoxicity Intron Exons Biology medicine.disease Polymerase Chain Reaction Receptors Neurotransmitter Europe Exon Excitatory Amino Acid Transporter 2 Neurology medicine Humans Coding region Electrophoresis Polyacrylamide Gel Neurology (clinical) Amyotrophic lateral sclerosis Gene Polymorphism Single-Stranded Conformational |
| Zdroj: | Journal of Neurology. 246:1140-1144 |
| ISSN: | 1432-1459 0340-5354 |
| DOI: | 10.1007/s004150050532 |
| Popis: | Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder characterised by degeneration of upper and lower motor neurons. Whilst the primary pathogenic trigger is unknown in most cases, evidence is mounting to implicate a role for glutamate-mediated neurotoxicity in the disorder. Recent studies have shown reduced levels of the mainly astroglial glutamate transporter EAAT2 in ALS motor cortex and spinal cord and multiple abnormal EAAT2 mRNA species in ALS brain tissue. One cause of the low EAAT2 levels may be that point mutations in the EAAT2 gene, EAAT2, result in an abnormal unstable protein. To test this hypothesis we analysed EAAT2 in 128 sporadic and 23 familial European ALS cases. No variants within the coding sequence of EAAT2 to affect the protein sequence nor in the consensus splice sites of the flanking intronic sequences were found in any cases, similar to findings in other reports. Frequent polymorphisms within the flanking intronic sequences of both exons 2 and 4 were seen but at similar frequencies in controls. Mechanisms other than mutations within the coding region of EAAT2 must therefore be responsible for the low levels of EAAT2 seen in most cases of ALS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink