Nat Genet：研究发现癫痫性脑病的新致病基因

癫痫性脑病是发生在婴儿和儿童的严重痉挛性疾病。这种癫痫性疾病会导致发育迟缓和智力障碍。一项大规模的科学研究发现一些新基因在婴儿期或儿童早期导致癫痫性疾病。这项发现将会开发诊断这些情况的新试验，及为改善结果带来希望。

来自墨尔本大学和费洛里研究所神经科学和心理健康的儿科神经学家和研究者，临床研究的领导者英格丽德佛教授说：“这些儿童患有破坏性的疾病。找出原因是开发有针对性的治疗的首要一步”。她说：“总的来说，我们的研究结果对诊断患者、优化治疗及为患者家人提供基因咨询有重要的启示”今天发布的这项研究，揭示了与这些严重癫痫症有关的两个新基因。

在这项研究中，研究者分析了患癫痫性脑病的500名儿童的基因。应用基因测试方面的研究进展，下一代基因面板的测序被实施。研究者分析了65个基因，其中19个基因已经被证明与癫痫性脑病有关，其余46个基因猜测可能会导致这些破坏性的疾病。

研究结果揭示，导致癫痫性脑病的基因突变在500名患者中发现52名（超出研究人群的10％）。65个基因中发现有15个发生了基因突变，包括2个新基因，CHD2和SYNGAP1，这两个基因未曾发现会导致癫痫性脑病。英格丽佛教授说：“这是一个非常令人激动的突破，给患这种疾病的孩子们的生活带来了显著的好处”。这些基因将会成为患这些癫痫症的儿童的诊断性测试，而且使他们家人的基因咨询成为可能。

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
Abstract
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.