■靶向下一代测序板(TNGSP)已成为全球临床实践的标准。而不是质疑癫痫患者下一代测序的必要性,当代大规模研究的重点是TNGSP的规模等因素,外显子组或全基因组测序相对于TNGSP的比较优势,以及临床的影响,电生理学,和人口统计学变量对基因测试性能的影响。本研究旨在阐明影响138例波兰癫痫患者TNGSP表现的人口统计学和临床因素,认识到基因检测在指导患者管理和治疗方面的关键作用。
■对波兹南一家遗传诊所的患者进行了回顾性分析,波兰,他在2020年至2022年期间在Invitae公司(美国)接受了商业基因组研究。根据首次癫痫发作的发病年龄定义患者组,癫痫发作类型,性别,癫痫的发烧依赖性,存在智力障碍或发育迟缓,MRI异常,以及畸形特征或先天性畸形的存在。癫痫发作分类遵循2017年ILAE标准。
■在138名患者中,30(21.7%)表现出致病性或可能的致病性变异,男性占20.7%,女性占22.5%。诊断表现与患者首次发作时的年龄和发作类型相关。在SCN1A中确定了主要变体,PRRT2、CDKL5、DEPDC5、TSC2和SLC2A1基因。此外,12个基因(CACNA1A,SCN2A,GRIN2A,KCNQ2,CHD2,DYNC1H1,NEXMIF,SCN1B,DDX3X,EEF1A2,NPRL3,UBE3A)表现出单个损坏实例。值得注意的是,在DEPDC5、SCN1A、TSC2、CDKL5、NPRL3、DYNC1H1、CHD2和DDX3X。
■鉴定的变体存在于先前在欧洲和非欧洲人群中识别的基因中。对不确定重要性变体(VUS)的彻底检查,特别关注基因拷贝数的变化,可能揭示更广泛的染色体畸变。女孩中X染色体连锁基因的病理变异相对频繁发生,值得进一步研究。挑战男性在X连锁癫痫中占主导地位的普遍观念。
UNASSIGNED: Targeted Next-Generation Sequencing Panels (TNGSP) have become a standard in global clinical practice. Instead of questioning the necessity of next-generation sequencing in epilepsy patients, contemporary large-scale research focuses on factors such as the size of TNGSP, the comparative advantages of exome or genome-wide sequencing over TNGSP, and the impact of clinical, electrophysiological, and demographic variables on genetic test performance. This study aims to elucidate the demographic and clinical factors influencing the performance of TNGSP in 138 Polish patients with epilepsy, recognizing the pivotal role of genetic testing in guiding patient management and therapy.
UNASSIGNED: A retrospective analysis was conducted on patients from a genetic clinic in Poznań, Poland, who underwent commercial gene panel studies at Invitae Corporation (USA) between 2020 and 2022. Patient groups were defined based on the age of onset of the first epileptic seizures, seizure type, gender, fever dependence of seizures, presence of intellectual disability or developmental delay, abnormalities in MRI, and the presence of dysmorphic features or congenital malformations. Seizure classification followed the 2017
ILAE criteria.
UNASSIGNED: Among the 138 patients, 30 (21.7%) exhibited a pathogenic or likely pathogenic variant, with a distribution of 20.7% in males and 22.5% in females. Diagnostic performance correlated with the patient\'s age at the onset of the first seizure and the type of seizure. Predominant variants were identified in the SCN1A, PRRT2, CDKL5, DEPDC5, TSC2, and SLC2A1 genes. Additionally, 12 genes (CACNA1A, SCN2A, GRIN2A, KCNQ2, CHD2, DYNC1H1, NEXMIF, SCN1B, DDX3X, EEF1A2, NPRL3, UBE3A) exhibited single instances of damage. Notably, novel variants were discovered in DEPDC5, SCN1A, TSC2, CDKL5, NPRL3, DYNC1H1, CHD2, and DDX3X.
UNASSIGNED: Identified variants were present in genes previously recognized in both European and non-European populations. A thorough examination of Variants of Uncertain Significance (VUSs), specifically focusing on gene copy number changes, may unveil more extensive chromosomal aberrations. The relatively frequent occurrence of pathological variants in X chromosome-linked genes in girls warrants further investigation, challenging the prevailing notion of male predominance in X-linked epilepsy.