Yarali Oğuzhan, Gündoğdu Öğütlü Özge Beyza, Saritaş Serdar, Guler Mustafa Can, Keskin Filiz, Türkyilmaz Ayberk
Department of Medical Genetics, Erzurum Regional Training and Research Hospital, Erzurum, Turkey.
Department of Pediatric Neurology, Erzurum Regional Training and Research Hospital, Erzurum, Turkey.
J Neurogenet. 2024 Sep;38(3):112-121. doi: 10.1080/01677063.2024.2424777. Epub 2024 Nov 17.
This study investigates the genetic causes of epilepsy in 166 paediatric patients under the age of 16 from the East Anatolian region of Turkey, who were treated at Erzurum City Hospital between 2018 and 2023. Patients with early-onset seizures, a family history of epilepsy or intellectual disability was selected for genetic analysis using a next-generation sequencing (NGS) gene panel targeting 449 genes associated with epilepsy and epileptic encephalopathy. The analysis revealed that pathogenic or probable pathogenic mutations were present in 14.8% (32 patients), highlighting the significant role of genetic factors in the aetiology of epilepsy in this population. In addition, 30.6% (66 patients) carried variants of uncertain significance (VUS), which, although not classified as pathogenic, have potential clinical relevance. Many epilepsy-related genes follow an autosomal dominant inheritance pattern, meaning that VUSs may gain pathogenic significance as more data and global studies accumulate, emphasising the evolving nature of genetic research. In addition to genetic factors, other aetiological causes such as perinatal insults (15.3%) and infections (7.9%) were identified, highlighting the multifactorial origin of epilepsy. While pathogenic mutations currently serve as important diagnostic and therapeutic markers, the role of VUS should not be underestimated. Genetic testing has proven to be essential for understanding the complex causes of epilepsy, providing opportunities for personalised treatment and genetic counselling. This study highlights the importance of genetic testing in regions such as Eastern Anatolia, where both environmental and genetic factors may influence the prevalence of epilepsy. As genetic databases expand, it is likely that the understanding of VUS will evolve, improving the clinical management of epilepsy through more targeted therapies and improved outcomes.
本研究调查了来自土耳其东安纳托利亚地区166名16岁以下儿科患者癫痫的遗传病因，这些患者于2018年至2023年在埃尔祖鲁姆市医院接受治疗。选择有早发性癫痫发作、癫痫家族史或智力残疾的患者，使用针对449个与癫痫和癫痫性脑病相关基因的下一代测序（NGS）基因panel进行遗传分析。分析显示，14.8%（32例患者）存在致病或可能致病的突变，突出了遗传因素在该人群癫痫病因中的重要作用。此外，30.6%（66例患者）携带意义未明的变异（VUS），这些变异虽然未被归类为致病，但具有潜在的临床相关性。许多与癫痫相关的基因遵循常染色体显性遗传模式，这意味着随着更多数据和全球研究的积累，VUS可能会获得致病意义，强调了遗传研究的不断发展性质。除了遗传因素外，还确定了其他病因，如围产期损伤（15.3%）和感染（7.9%），突出了癫痫的多因素起源。虽然致病突变目前是重要的诊断和治疗标志物，但VUS的作用不应被低估。基因检测已被证明对于理解癫痫的复杂病因至关重要，为个性化治疗和遗传咨询提供了机会。本研究强调了基因检测在东安纳托利亚等地区的重要性，在这些地区，环境和遗传因素都可能影响癫痫的患病率。随着遗传数据库的扩大，对VUS的理解可能会不断发展，通过更有针对性的治疗和改善预后，提高癫痫的临床管理水平。
