Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Key Laboratory of Pediatrics in Chongqing, Chongqing, China.
Mol Genet Genomic Med. 2019 Sep;7(9):e926. doi: 10.1002/mgg3.926. Epub 2019 Aug 8.
The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that lowers seizure threshold and may also enhance epileptogenesis. In this study, three patients diagnosed with SZT2-related developmental and epileptic encephalopathies (DEEs) were reviewed aiming to expand knowledge of the genotype and phenotype of SZT2 mutations.
Targeted next-generation sequencing was performed to identify pathogenic mutations in 205 cases with DEEs of unknown etiology. Detailed clinical and genetic data were collected from SZT2-associated patients.
Four novel mutations were found (c.1626 + 1G>A, c.5772dupA, c.4209C > A, c.7307_7308insG) in three patients. All the variants were inherited from their parents. Two patients were siblings and harbored the same mutations and presented developmental delay prior to the onset of seizures. All the individuals were diagnosed as DEEs, drug refractory epilepsy, and experienced status epilepticus (SE); one patient died of SE. One subject showed subependymal nodules as similar as those of tuberous sclerosis complex (TSC) in cranial magnetic resonance imaging (MRI).
Our results expand the genotype and phenotypes of SZT2-related DEEs, suggesting that SZT2 mutations play a role in developmental delay and epileptic encephalopathy, with high susceptibility to SE and relatively specific MRI findings.
癫痫发作阈 2（SZT2）基因编码一种大型、高度保守的蛋白质，可降低癫痫发作阈值，并可能增强癫痫发生。在这项研究中，对三名被诊断为 SZT2 相关发育性和癫痫性脑病（DEE）的患者进行了回顾，旨在扩展 SZT2 突变的基因型和表型知识。
对 205 例病因不明的 DEE 患者进行靶向下一代测序，以鉴定致病性突变。从 SZT2 相关患者中收集详细的临床和遗传数据。
在三名患者中发现了四个新的突变（c.1626+1G>A、c.5772dupA、c.4209C>A、c.7307_7308insG）。所有变异均来自父母遗传。两名患者是兄弟姐妹，携带相同的突变，并在癫痫发作前出现发育迟缓。所有患者均被诊断为 DEE、药物难治性癫痫，并经历癫痫持续状态（SE）；一名患者死于 SE。一名患者的头颅磁共振成像（MRI）显示类似于结节性硬化症（TSC）的室管膜下结节。
我们的结果扩展了 SZT2 相关 DEE 的基因型和表型，表明 SZT2 突变在发育迟缓及癫痫性脑病中起作用，对 SE 具有高易感性，并且具有相对特定的 MRI 发现。
