Abstract：
γ-Aminobutyric acid (GABA)A -receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of the common molecular structure and physiological role of these phenotypes, it seemed interesting to describe a putative phenotype associated with GABAA -receptor-related disorders as a whole and seek possible genotype-phenotype correlations.
We collected clinical, electrophysiological, therapeutic, and molecular data from patients with GABAA -receptor subunit variants (GABRA1, GABRB2, GABRB3, and GABRG2) through a national French collaboration using the EPIGENE network and compared these data to the one already described in the literature.
We gathered the reported patients in three epileptic phenotypes: 15 patients with fever-related epilepsy (40%), 11 with early developmental epileptic encephalopathy (30%), 10 with generalized epilepsy spectrum (27%), and 1 patient without seizures (3%). We did not find a specific phenotype for any gene, but we showed that the location of variants on the transmembrane (TM) segment was associated with a more severe phenotype, irrespective of the GABAA -receptor subunit gene, whereas N-terminal variants seemed to be related to milder phenotypes.
GABAA -receptor subunit variants are associated with highly variable phenotypes despite their molecular and physiological proximity. None of the genes described here was associated with a specific phenotype. On the other hand, it appears that the location of the variant on the protein may be a marker of severity. Variant location may have important weight in the development of targeted therapeutics.
We collected clinical, electrophysiological, therapeutic, and molecular data from patients with GABAA -receptor subunit variants (GABRA1, GABRB2, GABRB3, and GABRG2) through a national French collaboration using the EPIGENE network and compared these data to the one already described in the literature.
We gathered the reported patients in three epileptic phenotypes: 15 patients with fever-related epilepsy (40%), 11 with early developmental epileptic encephalopathy (30%), 10 with generalized epilepsy spectrum (27%), and 1 patient without seizures (3%). We did not find a specific phenotype for any gene, but we showed that the location of variants on the transmembrane (TM) segment was associated with a more severe phenotype, irrespective of the GABAA -receptor subunit gene, whereas N-terminal variants seemed to be related to milder phenotypes.
GABAA -receptor subunit variants are associated with highly variable phenotypes despite their molecular and physiological proximity. None of the genes described here was associated with a specific phenotype. On the other hand, it appears that the location of the variant on the protein may be a marker of severity. Variant location may have important weight in the development of targeted therapeutics.
摘要：
γ-氨基丁酸（GABA）A-受体亚基变体最近与神经发育障碍和/或癫痫有关。与每个基因相关的表型越来越为人所知。由于这些表型的共同分子结构和生理作用，从整体上描述与GABAA受体相关疾病相关的推定表型并寻找可能的基因型-表型相关性似乎很有趣.
我们收集了临床，电生理学,治疗性的,和来自GABAA受体亚基变异体(GABRA1,GABRB2,GABRB3和GABRG2)患者的分子数据,通过法国国家合作使用EPIGENE网络,并将这些数据与文献中已经描述的数据进行了比较.
我们收集了三种癫痫表型的报告患者：15例发热相关癫痫患者（40%），11患有早期发育性癫痫性脑病（30％），10例具有全身性癫痫谱（27%），1例患者无癫痫发作（3%）。我们没有发现任何基因的特定表型，但是我们发现跨膜（TM）片段上变异的位置与更严重的表型有关，与GABAA受体亚基基因无关，而N端变异似乎与轻度表型有关。
GABAA-受体亚基变体与高度可变的表型相关,尽管它们在分子和生理上接近。此处描述的基因均不与特定表型相关。另一方面,看来，蛋白质上变异的位置可能是严重程度的标志。变体位置在靶向治疗剂的开发中可能具有重要的重量。
我们收集了临床，电生理学,治疗性的,和来自GABAA受体亚基变异体(GABRA1,GABRB2,GABRB3和GABRG2)患者的分子数据,通过法国国家合作使用EPIGENE网络,并将这些数据与文献中已经描述的数据进行了比较.
我们收集了三种癫痫表型的报告患者：15例发热相关癫痫患者（40%），11患有早期发育性癫痫性脑病（30％），10例具有全身性癫痫谱（27%），1例患者无癫痫发作（3%）。我们没有发现任何基因的特定表型，但是我们发现跨膜（TM）片段上变异的位置与更严重的表型有关，与GABAA受体亚基基因无关，而N端变异似乎与轻度表型有关。
GABAA-受体亚基变体与高度可变的表型相关,尽管它们在分子和生理上接近。此处描述的基因均不与特定表型相关。另一方面,看来，蛋白质上变异的位置可能是严重程度的标志。变体位置在靶向治疗剂的开发中可能具有重要的重量。
