Genetics of generalized epilepsy

癫痫是发生癫痫的一组疾病的名称。5%的人会有至少一次癫痫发作。伴随发烧(发烧)的癫痫发作在儿童早期很常见。大多数形式的癫痫和发热性癫痫都有遗传成分。在寻找常见形式癫痫的基因方面进展缓慢，可能是因为它们是由于许多基因的相互作用所致。罕见癫痫的4个基因已被鉴定为单基因遗传。这些基因编码细胞中离子通道的亚单位。我们研究许多人有癫痫发作的家庭，并仔细诊断癫痫发作的类型。这项工作描述了5个新的遗传性癫痫，并发现了4个已知基因中的3个。最重要的新遗传性癫痫是全身性癫痫伴热性惊厥(GEFS+)。GEFS+是许多儿童发热性癫痫发作仅限于儿童早期，或癫痫发作持续到儿童期中期的原因。GEFS+家庭可能包括患有严重全身性癫痫伴智力残疾的个人。在一个患有GEFS+的塔斯马尼亚家庭中，我们发现大脑中神经细胞的钠通道存在基因缺陷。我们计划研究更多患有GEFS+的家庭。我们认为，特定的严重儿童期癫痫可能发生在GEFS+的家庭中。如果是这样，那么这些严重疾病的根本原因可能是GEFS+的基因缺陷。找到这样的基因将有助于了解癫痫发作的基础，并最终导致靶向治疗。我们关于GEFS+的工作的第二个主要重点是利用家族研究来了解不同类型的癫痫是如何遗传的，并获得对常见癫痫背后的基因相互作用的见解。我们计划研究GEFS+的孤立病例，寻找在家庭中发现的基因缺陷。这一策略将揭示相同的基因是否在常见癫痫的遗传学中起重要作用。

Epilepsy is the name of a group of disorders where seizures occur. 5% of people will have at least one seizure. Seizures accompanied by fever (febrile) are common in early childhood. Most forms of epilepsy and febrile seizures have an inherited component. Progress in finding genes for common forms of epilepsy has been slow, probably because they are due to the interaction of a number of genes. Four genes for rare epilepsies with single gene inheritance have been identified. These genes code for subunits of ion channels in cells. We study families where many individuals have seizures and carefully diagnose the seizures types. This work has resulted in the description of 5 new inherited epilepsies and led to discovery of 3 of the 4 known genes. The most important new inherited epilepsy is Generalized Epilepsy with Febrile Seizures Plus (GEFS+). GEFS+ accounts for many children with febrile seizures restricted to early childhood, or where seizures continue into mid-childhood. GEFS+ families may contain an individual with severe generalized epilepsy with intellectual disability. In a Tasmanian family with GEFS+, we found a gene defect in the sodium channel of nerve cells in the brain. We plan to study more families with GEFS+. We believe that specific severe childhood epilepsies may occur in families with GEFS+. If so, then the underlying cause of these serious disorders may be gene defects of GEFS+. Finding such genes will help to understand the basis of seizures and ultimately lead to targeted therapies. The second major focus of our work on GEFS+ is to use family studies to understand how different types of seizures are inherited, and to gain insights into the gene interactions underlying common epilepsies. We plan to study isolated cases of GEFS+ for the gene defects found in families. This strategy will reveal whether the same genes are important in the genetics of the common epilepsies.