Abstract：
The progressive myoclonus epilepsies (PMEs) are a heterogeneous group of neurodegenerative disorders, typically presenting in late childhood. An etiologic diagnosis is achieved in about 80% of patients with PME, and genome-wide molecular studies on remaining, well-selected, undiagnosed cases can further dissect the underlying genetic heterogeneity. Through whole-exome sequencing (WES), we identified pathogenic truncating variants in the IRF2BPL gene in two, unrelated patients presenting with PME. IRF2BPL belongs to the transcriptional regulators family and it is expressed in multiple human tissues, including the brain. Recently missense and nonsense mutations in IRF2BPL were found in patients presenting with developmental delay and epileptic encephalopathy, ataxia, and movement disorders, but none with clear PME. We identified 13 other patients in the literature with myoclonic seizures and IRF2BPL variants. There was no clear genotype-phenotype correlation. With the description of these cases, the IRF2BPL gene should be considered in the list of genes to be tested in the presence of PME, in addition to patients with neurodevelopmental or movement disorders.
摘要：
进行性肌阵挛性癫痫(PMEs)是一组异质性的神经退行性疾病,通常出现在儿童晚期。大约80％的PME患者获得了病因诊断，和全基因组分子研究，选得好,未确诊病例可以进一步剖析潜在的遗传异质性。通过全外显子组测序（WES），我们在两名出现PME的无关患者中鉴定了IRF2BPL基因的致病性截短变异.IRF2BPL属于转录调节因子家族，在多种人体组织中表达，包括大脑。最近在患有发育迟缓和癫痫性脑病的患者中发现了IRF2BPL的错义和无义突变，共济失调,运动障碍,但没有明确的PME。我们在文献中确定了13例其他患者患有肌阵挛性癫痫发作和IRF2BPL变异。没有明确的基因型-表型相关性。根据这些案例的描述,IRF2BPL基因应在PME存在下进行测试的基因列表中考虑，除了神经发育或运动障碍患者。
