Genetics of generalized epilepsy

全身性癫痫的遗传学

• 批准号: nhmrc : 145791
• 负责人: Prof Ingrid Scheffer
• 金额: $ 7.02万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/genetics-generalized-epilepsy/97899
• 关键词: Genetics; generalized; epilepsy

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.

癫痫是一组疾病的名称，其中癫痫发作发生。5%的人至少会发作一次。癫痫发作伴有发热（发热）在幼儿期很常见。大多数形式的癫痫和热性惊厥都有遗传成分。寻找常见癫痫病的基因进展缓慢，可能是因为它们是由于许多基因的相互作用。已经鉴定出四种具有单基因遗传的罕见癫痫基因。这些基因编码细胞中离子通道的亚基。我们研究了许多人癫痫发作的家庭，并仔细诊断癫痫发作的类型。这项工作导致了5种新的遗传性癫痫的描述，并导致了4种已知基因中的3种的发现。最重要的新遗传性癫痫是全身性癫痫伴热性惊厥+（GEFS+）。GEFS+解释了许多仅限于幼儿期的热性惊厥儿童，或惊厥持续到儿童中期的儿童。GEFS+家庭可能包含患有严重全身性癫痫伴智力残疾的个体。在一个患有GEFS+的塔斯马尼亚家庭中，我们发现大脑神经细胞钠通道的基因缺陷。我们计划通过GEFS+研究更多的家庭。我们认为，特定的严重儿童癫痫可能发生在家庭与GEFS+。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。找到这些基因将有助于了解癫痫发作的基础，并最终导致靶向治疗。我们在GEFS+上工作的第二个主要重点是使用家庭研究来了解不同类型的癫痫发作是如何遗传的，并深入了解常见癫痫的基因相互作用。我们计划研究GEFS+的孤立病例，以寻找在家族中发现的基因缺陷。这一策略将揭示相同的基因是否在常见癫痫的遗传学中是重要的。