Reanalysis of whole exome sequencing data in patients with epilepsy and intellectual disability/mental retardation
Reanalysis of whole exome sequencing data in patients with epilepsy and intellectual disability/mental retardation
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癫痫合并智力障碍/精神发育迟滞患者全外显子组测序数据的再分析
DOI：
10.1016/j.gene.2019.03.037
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发表时间：
2019-06-05
期刊：
影响因子：
3.5
通讯作者：
Jiang, Yuwu
中科院分区：
文献类型：
--
作者：
Li, Jinliang;Gao, Kai;Jiang, Yuwu
为了评估全外显子组测序 (WES) 重新分析对癫痫和智力障碍/精神发育迟滞患者的额外诊断效果，我们重新分析了 76 名初始报告返回阴性结果的患者的原始 WES 数据和临床信息。 8名患者（10.5%，8/76）最终基因诊断呈阳性，其中5个基因有6个新突变。此前假阴性报告的原因分为四类：首次报告时尚未建立特定基因疾病关联；基因检测中心疾病数据库未及时更新；在应用基因检测和分析变异时，没有仔细或正确地收集、提交和审查患者的临床表型；第一轮数据分析漏掉了影响剪接的同义变异。因此，医生在自行或与基因检测中心的生物信息学专家合作重新检查WES数据和临床表型之前，不应放弃致病突变的发现，尤其是对于最初WES结果为“阴性”的疑似遗传病患者。重新分析的合适时间点可能是初次报告后的 6-12 个月。
To evaluate the additional diagnostic yield of whole exome sequencing (WES) reanalysis in patients with epilepsy and intellectual disability/mental retardation, we reanalyzed raw WES data and clinical information for 76 patient trios whose initial reports returned negative results. Eight patients (10.5%, 8/76) had positive genetic diagnoses finally, including six novel mutations in five genes. The reasons for the previous false-negative reports were divided into four categories: specific gene disease associations had not been established at the time of the initial report; the disease database of the genetic test center had not been updated in a timely manner; the patient's clinical phenotype had not been carefully or correctly collected, submitted and reviewed when applicating genetic test and analyzing the variants; and the first round of data analysis missed a synonymous variant that affected splicing. Therefore, physicians should not give up the discovery of disease-causing mutations before re-examining the WES data and clinical phenotype by themselves or by collaborating with bioinformatic experts in the genetic test centers, especially for patients with strongly suspected genetic disease whose initial WES result was "negative". The suitable time points for reanalysis might be the 6-12 months after initial report.