Detection of copy number variations in epilepsy using exome data
Detection of copy number variations in epilepsy using exome data
复制标题
DOI：
10.1111/cge.13144
复制
发表时间：
2018-03-01
影响因子：
3.5
通讯作者：
Matsumoto, N.
中科院分区：
文献类型：
--
作者：
Tsuchida, N.;Nakashima, M.;Matsumoto, N.
癫痫是一种常见的神经系统疾病，其发病机制与遗传因素有关。拷贝数变异（CNVs）越来越被认为是包括癫痫在内的许多人类疾病的重要病因。全外显子组测序（WES）正在成为检测致病性突变的标准工具，最近已被应用于检测CNV。在这里，我们使用WES分析了294个癫痫家族，并集中在168个已知癫痫相关基因中没有致病性单核苷酸变异的家族中，以使用2种不同的CNV检测工具使用WES数据进一步验证CNV。我们证实了18个致病性CNV，2个缺失和2个重复在chr15q11.2的临床意义不明。值得注意的是，我们能够识别小于10kb的小CNV，这可能难以通过常规微阵列检测到。我们发现了2例致病性CNV，2种CNV检测工具之一未能发现，这表明建议使用不同的CNV工具来提高诊断率。考虑到相对高的CNV发现率（168个家族中的18个，10.7%）和成功检测CNV，
Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) are increasingly recognized as an important etiology of many human diseases including epilepsy. Whole-exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations and has recently been applied to detecting CNVs. Here, we analyzed 294 families with epilepsy using WES, and focused on 168 families with no causative single nucleotide variants in known epilepsy-associated genes to further validate CNVs using 2 different CNV detection tools using WES data. We confirmed 18 pathogenic CNVs, and 2 deletions and 2 duplications at chr15q11.2 of clinically unknown significance. Of note, we were able to identify small CNVs less than 10kb in size, which might be difficult to detect by conventional microarray. We revealed 2 cases with pathogenic CNVs that one of the 2 CNV detection tools failed to find, suggesting that using different CNV tools is recommended to increase diagnostic yield. Considering a relatively high discovery rate of CNVs (18 out of 168 families, 10.7%) and successful detection of CNV with