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Objective@#To summarize the clinical phenotypes of epilepsy in patients with GABRA1 gene variants.@*Methods@#A total of 11 epileptic patients (4 boys and 7 girls) who were treated in the Department of Pediatrics, Peking University First Hospital from March 2016 to July 2019 and detected with GABRA1 gene heterozygous pathogenic variants by targeted next-generation sequencing were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively.@*Results@#A total of 11 epileptic patients carried GABRA1 gene pathogenic variants, of whom 10 were de novo variants and the other one was inherited from the patient′s mother. Two patients had the same variants. Six variants were novel. Ages at seizure onset ranged from 3 to 14 months, and the median age was 8 months. The seizure was first observed within 1 year in 10 patients and beyond 1 year of age in 1 patient. Multiple seizure types were observed, including focal seizures in 10 patients, generalized tonic clonic seizures (GTCS) in 3 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. There were 5 patients with multiple seizure types. Sensitivity to fever was observed in 9 patients, among whom 6 patients had a history of status epilepticus. Two patients had photoparoxysmal response. Five patients had abnormal EEG background, and 6 patients had abnormal discharges in EEG during interictal phase. Brain magnetic resonance imaging (MRI) was normal in all patients. Developmental delay in various degrees was present in 9 patients. Among the 11 patients, Dravet syndrome was diagnosed in 5 patients, West syndrome in 2 patients, undiagnosed early-onset epileptic encephalopathy in 1 patient, and focal epilepsy in the other 3 patients. The ages at the last follow-up ranged from 8 months to 12 years. During follow-up, 8 patients were seizure-free for 6 months to 8 years, and 1 patient had discontinuation of medication.@*Conclusions@#In epilepsy associated with GABRA1 gene variants, de novo pathogenic variants are more common than inherited. Most epilepsy caused by GABRA1 gene variants occurs in infancy. Most patients have multiple seizures and focal seizures are common. Most patients have a comparatively favorable prognosis, but they may still have varied degrees of developmental delay.
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OBJECTIVE: The genes encoding for gamma-aminobutyric acid (GABA) A and B receptors may be considered as candidates for alcoholism; genetic alterations at this level may produce structural and functional diversity and thus play a role in the response to alcohol addiction treatment. To investigate these aspects further, we conducted a preliminary genetic association study on a population of Italian male alcohol addicts, focusing on GABA A and B receptors. METHODS: A total of 186 alcohol-dependent subjects (in the first phase 139, then 47 more samples) and 182 controls were genotyped for 25 single nucleotide polymorphisms (SNPs) of genes encoding the alpha-1 subunit of GABA A receptor (GABRA1) and subunits 1 and 2 of GABA B receptor (GABBR1 and GABBR2). The chi-squared test for allele and genotype distributions and Hardy-Weinberg equilibrium analysis of both subjects and controls were performed. Bonferroni's correction for multiple comparisons was applied. RESULTS: Preliminary results comparing 139 alcohol-dependent subjects and 182 controls showed differences in genotype distribution in the former for SNP rs29253, located in the intron region of the GABBR1 gene. In order to clarify the meaning of this association, 47 more samples from alcohol-dependent subjects were tested for this SNP only: the previously found association was not confirmed. CONCLUSION: The lack of significant differences between the two groups does not provide evidence that GABRA 1 and GABBR1 and 2 genes are candidates for alcoholism in this population. Further studies with larger samples are needed, together with investigation of other components of the GABA pathway.