Zara F, Bianchi A, Avanzini G, Di Donato S, Castellotti B, Patel P I, Pandolfo M
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Hum Mol Genet. 1995 Jul;4(7):1201-7. doi: 10.1093/hmg/4.7.1201.
Idiopathic generalized epilepsy (IGE) is characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Twin and family studies suggest that genetic factors play a key part in IGE. A multilocus model appears to best fit the observed inheritance patterns. Mapping of IGE-related genes has been previously attempted using parametric methods, with conflicting results. In particular, recent evidence argues both for and against a chromosome 6p locus (EJM1) for juvenile myoclonic epilepsy, a subtype of IGE. We have approached the problem of mapping IGE loci using non-parametric methods, which have recently been successful for other complex diseases. No evidence for linkage to chromosome 6p was obtained. However, we obtained evidence for involvement of a locus at chromosome 8q24, close to the marker D8S256. The same 8q24 region was previously implicated in families with benign neonatal familial convulsions (BNFC), a generalized epilepsy syndrome that is inherited as a simple dominant mendelian trait. There is an apparent conserved syntenic group of genes in human 8q24 and a region of mouse chromosome 15, which harbors the stargazer (stg) locus. Homozygous mutant mice at the stg locus show a form of generalized epilepsy that resembles human absence epilepsy. Our findings may have implications for a locus on 8q24 predisposing to IGE.
特发性全身性癫痫（IGE）的特征是在没有可检测到的脑损伤和/或代谢异常的情况下反复出现全身性癫痫发作。双胞胎和家族研究表明，遗传因素在IGE中起关键作用。多位点模型似乎最符合观察到的遗传模式。先前曾尝试使用参数方法对IGE相关基因进行定位，但结果相互矛盾。特别是，最近有证据支持和反对将6号染色体p位点（EJM1）与青少年肌阵挛性癫痫（IGE的一种亚型）相关联。我们使用非参数方法来解决IGE基因座的定位问题，该方法最近在其他复杂疾病研究中取得了成功。未获得与6号染色体p位点连锁的证据。然而，我们获得了证据，表明8号染色体q24位点（靠近标记D8S256）与之相关。之前在患有良性新生儿家族性惊厥（BNFC）的家族中也发现了相同的8q24区域，BNFC是一种作为简单显性孟德尔性状遗传的全身性癫痫综合征。在人类8q24和小鼠15号染色体的一个区域中存在一个明显保守的同线基因群，该区域包含stargazer（stg）基因座。stg基因座的纯合突变小鼠表现出一种类似于人类失神性癫痫的全身性癫痫形式。我们的发现可能对8q24上易患IGE的基因座有影响。
