Systems and Computational Biology, Bio21 Institute, University of Melbourne, Parkville, VIC 3052, Australia.
Computational Biology and Clinical Informatics, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Int J Mol Sci. 2023 Mar 7;24(6):5114. doi: 10.3390/ijms24065114.
Developmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms that sometimes lead to death. Although previous work successfully discovered several genes implicated in disease outcomes, it remains challenging to identify causative mutations within these genes from the background variation present in all individuals due to disease heterogeneity. Nevertheless, our ability to detect possible pathogenic variants has continued to improve as predictors of deleteriousness have advanced. We investigate their use in prioritising likely pathogenic variants in epileptic encephalopathy patients' whole exome sequences. We showed that the inclusion of structure-based predictors of intolerance improved upon previous attempts to demonstrate enrichment within epilepsy genes.
发育性和癫痫性脑病（DEEs）是一组具有早发性和严重症状的癫痫，有时会导致死亡。尽管以前的工作成功发现了几个与疾病结果相关的基因，但由于疾病异质性，要从所有个体中存在的背景变异中识别出这些基因中的致病突变仍然具有挑战性。尽管如此，随着有害性预测因子的不断发展，我们检测可能的致病性变异的能力也在不断提高。我们研究了它们在优先考虑癫痫性脑病患者全外显子序列中可能的致病性变异中的用途。我们表明，包含基于结构的不耐受性预测因子可改善以前在癫痫基因中进行富集的尝试。
