Genetic analysis of the GABRA1 gene in patients with essential tremor.
The gamma-aminobutyric acid A (GABA-A) receptor mediates inhibitory neurotransmission in the brain and as such may be involved in certain neurological movement disorders, such as tremor. GABA-A receptor alpha 1 (Gabra)(-/-) mice have been reported to exhibit postural and kinetic, alcohol-responsive, tremor that is characteristic of essential tremor (ET), the most common form of tremor. To determine whether ET is associated with the GABRA1 gene mutation, we screened 76 patients with familial ET and found a novel nucleotide variant: IVS8+24 G>T (nt 6119289) in a male patient, and a known 156T>C polymorphism (nt 6090903) in exon 4 in 41% patients, which results in a silent mutation (G52G). No significant association between 156T>C variant and disease risk was found (adjusted OR=0.95, 95% CI=0.57-1.61; p=0.858) by further analysis of 121 familial ET patients and 114 normal controls, except a novel 96A>G (Q32Q; nt 6090743) variant, found in a normal control. Since the 156T>C variant appears to be not pathogenically relevant, our results suggest that missense, nonsense or splice site mutation in the coding region of the GABRA1 gene is not a major genetic cause of ET in Caucasian subjects.
Deng
Hao
H
Department of Neurology, Baylor College of Medicine, 6501 Fannin Street, Houston, TX 77030, USA.
Xie
Wen-Jie
WJ
Le
Wei-Dong
WD
Huang
Mao-Sheng
MS
Jankovic
Joseph
J
D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004252:DNA Mutational Analysis; D020329:Essential Tremor / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C546240:GABRA1 protein, human; C546241:Gabra1 protein, mouse; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid