Genetic study of epilepsies and febrile convulsions

本报告总结了我们自己发现的各种癫痫表型基因的新突变，以及突变基因的功能分析的主要结果。作为良性家族性新生儿惊厥（BFNC）的一个原因，我们发现了KCNQ2和KCNQ3突变。BFNC的年龄依赖性发展和自发性缓解的致病机制与新生儿中枢神经系统中抑制性kcnq通道活性的年龄依赖性降低和gaba能系统从兴奋作用到抑制作用的年龄依赖性功能转换之间的相互作用有关。与常染色体显性夜间额叶癫痫相关的神经元烟碱乙酰胆碱受体α4亚基Ser284Leu突变导致大鼠卵母细胞中表达的受体脱敏更快。我们在JME家族的6p12-p11染色体EJM1区域发现了一个新基因（贡献），并在舞蹈病-棘细胞增生症患者中发现了一个以前未知的全长cDNA，编码一种可能的结构蛋白，我们将其命名为chorein。我们报道了常染色体显性癫痫伴热性惊厥和婴儿期严重肌阵挛性癫痫与编码GABA-A受体（GABRG2）的Na^+通道亚基（SCN1A, SCN2A）和γ - 2亚基的各种基因突变相关。拉福素（一种主要与多核糖体相关的细胞质蛋白）是一种双特异性磷酸酶，由拉福拉病中存在缺陷的EPM2A基因编码。EPM2A外显子1突变与早发性认知缺陷亚表型相关。负责癫痫常见表型的基因尚未被发现，但毫无疑问，这些基因很快就会被发现。

This report summarizes our own discoveries of novel mutations in the genes of various epilepsy phenotypes, and of the main results of functional analyses of the mutated genes.As a cause of benign familial neonatal convulsions (BFNC), we identified mutations of KCNQ2 and KCNQ3. The pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC are associated with the interaction between age-dependent reduction of inhibitory KCNQ-channel activity and age-dependent functional switching of GABAergic-system from excitatory to inhibitory action in neonatal CNS. A mutation (Ser284Leu) of neuronal nicotinic acetylcholine receptor α4 subunit associated with autosomal dominant nocturnal frontal lobe epilepsy caused faster desensitization of rat receptor expressed in oocytes.We identified a novel gene in the EJM1 region on chromosome 6p12-p11 in families with JME (in contribution), and also identified a previously unknown, full-length of cDNA encoding a presumably structural protein, which we named chorein, in patients with chorea-acanthocytosis.We reported that autosomal dominant epilepsy with febrile seizure plus and severe myoclonic epilepsy of infancy were associated with various mutations of genes encoding both Na^+ channel subunit (SCN1A, SCN2A) and γ2-subunit of the GABA-A receptor (GABRG2).Laforin (a cytoplasmic protein associated primarily with polyribosome) is a dual-specificity phosphatase coded by the EPM2A gene defective in Lafora's disease. Exon 1 mutations of EPM2A was associated with an early-onset cognitive deficit subphenotype.Genes responsible for common phenotypes of epilepsy have been uncovered yet, however, these will undoubtedly be discovered soon.