Yudan Lv, Zan Wang, Chang Liu, Li Cui

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.