Phenotypic Spectrum and Prognosis of Epilepsy Patients With GABRG2 Variants

作者：Ying Yang, Xueyang Niu, Miaomiao Cheng, Qi Zeng, Jie Deng, Xiaojuan Tian, Yi Wang, Jing Yu, Wenli Shi, Wenjuan Wu, Jiehui Ma, Yufen Li, Xiaoling Yang, Xiaoli Zhang, Tianming Jia, Zhixian Yang, Jianxiang Liao, Yan Sun, Hong Zheng, Suzhen Sun, Dan Sun, Yuwu Jiang, Yuehua Zhang · 发表于：Frontiers in Molecular Neuroscience · 年份：2022 · DOI：10.3389/fnmol.2022.809163 · 被引用次数：20 · 研究领域：Genomics and Rare Diseases、Epilepsy research and treatment、Neurological diseases and metabolism

Objective This study aimed to obtain a comprehensive understanding of the genetic and phenotypic aspects of GABRG2 -related epilepsy and its prognosis and to explore the potential prospects for personalized medicine. Methods Through a multicenter collaboration in China, we analyzed the genotype-phenotype correlation and antiseizure medication (ASM) of patients with GABRG2 -related epilepsy. The three-dimensional protein structure of the GABRG2 variant was modeled to predict the effect of GABRG2 missense variants using PyMOL 2.3 software. Results In 35 patients with GABRG2 variants, 22 variants were de novo , and 18 variants were novel. The seizure onset age was ranged from 2 days after birth to 34 months (median age: 9 months). The seizure onset age was less than 1 year old in 22 patients (22/35, 62.9%). Seizure types included focal seizures (68.6%), generalized tonic-clonic seizures (60%), myoclonic seizures (14.3%), and absence seizures (11.4%). Other clinical features included fever-sensitive seizures (91.4%), cluster seizures (57.1%), and developmental delay (45.7%). Neuroimaging was abnormal in 2 patients, including dysplasia of the frontotemporal cortex and delayed myelination of white matter. Twelve patients were diagnosed with febrile seizures plus, eleven with epilepsy and developmental delay, two with Dravet syndrome, two with developmental and epileptic encephalopathy, two with focal epilepsy, two with febrile seizures, and four with unclassified epilepsy. The prop...