PEDEGO Research Unit, University of Oulu, Oulu, Finland; Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Department of Children and Adolescents, Division of Pediatric Neurology, Oulu University Hospital, Oulu, Finland.
Epilepsy and Clinical Neurophysiology, Children's National Health System, Washington, DC, USA.
Seizure. 2019 Jul;69:99-104. doi: 10.1016/j.seizure.2019.03.010. Epub 2019 Mar 19.
Next-generation sequencing (NGS) has made genetic testing of patients with epileptic encephalopathies easier - novel variants are discovered and new phenotypes described. Variants in the same gene - even the same variant - can cause different types of epilepsy and neurodevelopmental disorders. Our aim was to identify the genetic causes of epileptic encephalopathies in paediatric patients with complex phenotypes.
NGS was carried out for three patients with epileptic encephalopathies. Detailed clinical features, brain magnetic resonance imaging and electroencephalography were analysed. We searched the Human Gene Mutation Database for the published GABRG2 variants with clinical description of patients and composed a summary of the variants and their phenotypic features.
We identified two novel de novo GABRG2 variants, p.P282T and p.S306F, with new phenotypes including neuroradiological evidence of neurodegeneration and epilepsy of infancy with migrating focal seizures (EIMFS). One patient carried previously reported p.P83S variant with autism spectrum disorder (ASD) phenotype that has not yet been described related to GABRG2 disorders and a more severe epilepsy phenotype than reported earlier. In all, the literature search yielded twenty-two articles describing 27 different variants that were divided into two categories: those with self-limiting epilepsies and febrile seizures and those with more severe drug-resistant epileptic encephalopathies.
This study further expands the genotypic and phenotypic spectrum of epilepsies associated with GABRG2 variants. More knowledge is still needed about the influence of the environment, genetic background and other epilepsy susceptibility genes on the phenotype of the specific GABRG2 variants.
下一代测序（NGS）使癫痫性脑病患者的基因检测变得更加容易 - 新的变异被发现，新的表型被描述。同一基因中的变异 - 甚至是相同的变异 - 可能导致不同类型的癫痫和神经发育障碍。我们的目的是确定具有复杂表型的儿科癫痫性脑病患者的遗传原因。
对 3 例癫痫性脑病患者进行了 NGS。详细分析了临床特征、脑磁共振成像和脑电图。我们在人类基因突变数据库中搜索了具有患者临床描述的已发表的 GABRG2 变异，并对变异及其表型特征进行了总结。
我们发现了两个新的从头发生的 GABRG2 变异，p.P282T 和 p.S306F，具有新的表型，包括神经放射学证据的神经退行性变和婴儿期癫痫伴游走性局灶性发作（EIMFS）。一名患者携带先前报道的 p.P83S 变异，伴有自闭症谱系障碍（ASD）表型，尚未描述与 GABRG2 疾病相关的表型，且癫痫表型比以前报道的更严重。总共，文献检索得到了 22 篇文章，描述了 27 种不同的变异，分为两类：具有自限性癫痫和热性惊厥的变异，以及具有更严重的耐药性癫痫性脑病的变异。
本研究进一步扩大了与 GABRG2 变异相关的癫痫的基因型和表型谱。关于环境、遗传背景和其他癫痫易感性基因对特定 GABRG2 变异表型的影响，仍需要更多的知识。
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