Division of Morphogenesis, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Japan.
Am J Hum Genet. 2011 Feb 11;88(2):138-49. doi: 10.1016/j.ajhg.2010.12.012. Epub 2011 Feb 3.
Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution.
癫痫是遗传性的，但很少有明确的致病基因突变，迄今为止，尚未发现人类癫痫基因突变会导致无脊椎动物癫痫发作。在这里，我们表明，刺蛋白基因突变与人类、小鼠和果蝇的癫痫发作有关。我们鉴定出人类癫痫患者存在 PRICKLE1 或 PRICKLE2 中的杂合突变。在斑马鱼的过表达实验中，刺蛋白突变导致刺蛋白功能异常。Prickle1 缺失突变小鼠、两种 Prickle1 点突变（错义和无义）小鼠和 Prickle2 缺失突变小鼠均表现出癫痫表型。具有刺蛋白突变的果蝇表现出对抗癫痫药物有反应的癫痫发作，并且纯合突变胚胎显示出神经元缺陷。这些结果表明，刺蛋白突变在整个进化过程中导致了癫痫发作。
