Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics Department of Pediatrics, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany.
Center of Human Genetics and Laboratory Diagnostics, Martinsried, Germany.
Neuropediatrics. 2021 Apr;52(2):92-97. doi: 10.1055/s-0040-1712488. Epub 2020 Oct 21.
Next generation sequencing (NGS) with customized gene panels is a helpful tool to identify monogenic epilepsy syndromes. The number of genes tested within a customized panel may vary greatly. The aim of the present study was to compare the diagnostic yield of small (<25 kb) and large (>25 kb) customized epilepsy panels.
This retrospective cohort study investigated data of 190 patients of 18 years or younger, with the diagnosis of an epilepsy of unknown etiology who underwent NGS using customized gene panels. Small (<25 kb) and large (>25 kb) panels were compared regarding the distribution of benign/likely benign and pathogenic/likely pathogenic variants and variants of unclear significance. In addition, differences of the diagnostic yield with respect to epilepsy severity, i.e., developmental and epileptic encephalopathy [DEE] vs. non-DEE, were analyzed.
The diagnostic yield defined as pathogenic or likely pathogenic variants in large panels was significantly increased (29% [ = 14/48] vs. 13% [ = 18/142], = 0.0198) compared with smaller panels. In non-DEE patients the increase of the diagnostic yield in large panels was significant(35% = 6/17 vs. 13% = 12/94, = 0.0378), which was not true for DEE patients.
This study indicates that large panels are superior for pediatric patients with epilepsy forms without encephalopathy (non-DEE). For patients suffering from DEE small panels of a maximum of 10 genes seem to be sufficient. The proportion of unclear findings increases with rising panel sizes.
Customized epilepsy panels of >25 kb compared with smaller panels show a significant higher diagnostic yield in patients with epilepsy especially in non-DEE patients.
下一代测序（NGS）与定制基因面板是识别单基因癫痫综合征的有用工具。定制面板中测试的基因数量可能有很大差异。本研究的目的是比较小（<25kb）和大（>25kb）定制癫痫面板的诊断效果。
本回顾性队列研究调查了 190 名 18 岁以下病因不明的癫痫患者的 NGS 数据，这些患者使用定制基因面板进行 NGS。比较了小（<25kb）和大（>25kb）面板之间良性/可能良性和致病性/可能致病性变体以及意义不明变体的分布。此外，还分析了癫痫严重程度（即发育性和癫痫性脑病[DEE]与非 DEE）对诊断效果的差异。
大面板中致病性或可能致病性变体的诊断率明显增加（29% [=14/48] 比 13% [=18/142]，=0.0198）。在非 DEE 患者中，大面板的诊断率增加具有统计学意义（35% [=6/17] 比 13% [=12/94]，=0.0378），但在 DEE 患者中并非如此。
本研究表明，对于没有脑病（非 DEE）的癫痫患者，大面板优于小面板。对于患有 DEE 的患者，最大 10 个基因的小面板似乎就足够了。随着面板尺寸的增加，未明确发现的比例增加。
与小面板相比，>25kb 的定制癫痫面板在癫痫患者中尤其是在非 DEE 患者中显示出显著更高的诊断效果。
