Investigation of pathology for progressive myoclonus epilepsy

LD是一种致死性常染色体隐性遗传性癫痫，其特征为刺激敏感性肌阵挛、癫痫大发作以及进行性智力和神经功能退化。据报道，EPM2A基因与LD有关。我们在LD患者中发现了多种疾病EPM2A突变，并确定了一个LD亚类，该亚类显示出早发性认知缺陷并与EPM2A外显子1突变相关。我们报道了由EPM2A基因编码的laforin蛋白具有双特异性磷酸酶活性，与多聚核糖体结合，并与具有NifU样结构域的HIRIP5蛋白相互作用。我们最近产生并报道了EPM2A KO小鼠，这些小鼠发生神经变性和其他与LD患者相似的特征。

LD is a fatal autosomal recessive epilepsy characterized by stimuli sensitive myoclonus, grand mal seizures, and progressive intellectual and neurological deterioration. The EPM2A gene has been reported to be responsible for LD. We found multiple disease mutations of EPM2A in LD patients, and also identified a subclass of LD who shows an early onset cognitive defect and correlated with EPM2A exon 1 mutations. We reported that the laforin protein encoded by the EPM2A gene has a dual-specificity phosphatase activity, associates with polyribosome, and interacts with the HIRIP5 protein with NifU-like domain. We recently generated and reported the EPM2A KO mice those develop neurodegeneration and other features similar to those of LD patients.