Lv Yudan, Wang Zan, Liu Chang, Cui Li
Department of Neurology, Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, People's Republic of China.
Neuropsychiatr Dis Treat. 2017 Oct 19;13:2631-2636. doi: 10.2147/NDT.S145774. eCollection 2017.
Progressive myoclonic epilepsy (PME) is a heterogeneous neurodegenerative disorder, which is commonly manifested with refractory seizures and neurologic deterioration. The prognosis of PME is poor, so early diagnosis of PME is critical. The aim of our study is to identify the novel pathogenic gene in a Chinese family with PME, which may be helpful in future.
A three-generation consanguineous Chinese Han family with PME was recruited. A novel homozygous variant was identified by the genetic technique of exome sequencing and certificated by Sanger sequencing and functional prediction.
A novel homozygous variant, c.6975_6976insCAG, in the CACNA1A was identified in the PME family. The novel variant encoding the alpha-1A subunit of the calcium channel Cav2.1 was found in two siblings in the Chinese family and was absent in 50 normal controls. Our research indicates that the homozygous c.6975_6976insCAG might be the pathogenic mutation for PME.
As a molecular diagnostic strategy, our research explores the mutation gene spectrum of PME and has resulted in significant predictions for genetic counseling.
进行性肌阵挛癫痫（PME）是一种异质性神经退行性疾病，通常表现为难治性癫痫发作和神经功能恶化。PME的预后较差，因此早期诊断PME至关重要。我们研究的目的是在一个患有PME的中国家系中鉴定新的致病基因，这可能对未来有所帮助。
招募了一个患有PME的三代近亲中国汉族家系。通过外显子组测序的基因技术鉴定出一个新的纯合变异，并通过桑格测序和功能预测进行了验证。
在该PME家系中鉴定出CACNA1A基因中的一个新的纯合变异c.6975_6976insCAG。在中国家系的两个兄弟姐妹中发现了编码钙通道Cav2.1的α-1A亚基的新变异，而在50名正常对照中未发现。我们的研究表明，纯合的c.6975_6976insCAG可能是PME的致病突变。
作为一种分子诊断策略，我们的研究探索了PME的突变基因谱，并对遗传咨询产生了重要的预测。
