Sourbron Jo, Jansen Katrien, Mei Davide, Hammer Trine Bjørg, Møller Rikke S, Gold Nina B, O'Grady Lauren, Guerrini Renzo, Lagae Lieven
Department of Development and Regeneration, Section Pediatric Neurology, University Hospital KU Leuven, Leuven, Belgium.
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Neuropediatrics. 2022 Feb;53(1):46-51. doi: 10.1055/s-0041-1739133. Epub 2021 Dec 6.
We report an in-depth genetic analysis in an 11-year-old boy with drug-resistant, generalized seizures and developmental disability. Three distinct variants of unknown clinical significance (VUS) were detected by whole exome sequencing (WES) but not by initial genetic analyses (microarray and epilepsy gene panel). These variants involve the , and genes, which were subsequently evaluated by computational analyses using the InterVar tool and MutationTaster. While future functional studies are necessary to prove the pathogenicity of a certain VUS, segregation analyses over three generations and predictions suggest the X-linked gene (transmembrane solute carrier transporter) as the likely culprit gene in this patient. In addition, a search via GeneMatcher unveiled two additional patients with a VUS in . We propose as a likely candidate gene for epilepsy and/or developmental/cognitive delay and provide an overview of the 27 genes related to epilepsy by other preclinical and/or clinical studies.
我们报告了对一名11岁患有耐药性全身性癫痫发作和发育障碍男孩的深入基因分析。通过全外显子组测序（WES）检测到三个临床意义不明的不同变异（VUS），但初始基因分析（微阵列和癫痫基因panel）未检测到。这些变异涉及 、 和 基因，随后使用InterVar工具和MutationTaster通过计算分析对其进行了评估。虽然未来需要进行功能研究来证明某个VUS的致病性，但三代人的分离分析和 预测表明，X连锁基因 （跨膜溶质载体转运蛋白）可能是该患者的致病基因。此外，通过GeneMatcher搜索发现另外两名患者在 中有VUS。我们提出 作为癫痫和/或发育/认知延迟的可能候选基因，并概述了其他临床前和/或临床研究中与癫痫相关的27个 基因。
