Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE.
Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE.
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DOI：
10.1111/cge.13848
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发表时间：
2020-12
影响因子：
3.5
通讯作者：
Lee BH
中科院分区：
文献类型：
--
作者：
Seo GH;Kim T;Choi IH;Park JY;Lee J;Kim S;Won DG;Oh A;Lee Y;Choi J;Lee H;Kang HG;Cho HY;Cho MH;Kim YJ;Yoon YH;Eun BL;Desnick RJ;Keum C;Lee BH
EVIDENCE 是一种自动变异优先级系统，旨在促进全外显子组测序分析。本研究调查了证据对疑似遗传性疾病患者的诊断率。对 330 名疑似遗传性疾病先证者（年龄范围，0-68 岁）的 DNA 进行了全外显子组测序。候选变异通过证据进行鉴定，并通过测试家庭成员和/或临床重新评估进行确认。 EIDENCE 报告称，330 名先证者中的 200 名（60.6%）总共有 228 种变异。每名患者平均受累器官数量为4.5±5.0。经过临床重新评估和/或家庭成员测试后，在 141 名先证者 (42.7%) 中鉴定出 167 种变异，其中包括 105 种新变异。这些变异被证实与 121 种遗传性疾病有关。在临床评估和/或家庭成员检测之前，95 名患者的 167 种变异中有 103 种（61.7%）被归类为致病性或可能致病，137 名患者（41.5%）中有 161 种（96.4%）变异在临床评估和/或家庭成员检测后被归类为致病性或可能致病。与被视为致病的变异相关的因素包括基因变异与患者表型相似的症状评分。这种新的自动化变异解释系统促进了各种遗传疾病的诊断，诊断率为 42.7%。示意图显示有和没有变异鉴定和家庭成员检测的患者人数以及变异分类的比例。
EVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0‐68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom scores of a gene variant to the phenotype of the patient. This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 42.7% diagnostic yield. Schematic diagram showing the number of patients with and without variant identification and family member testing and the proportion of variant classification.
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影响因子：
3.4
作者：
Hoffman-Andrews, Lily
通讯作者：
Hoffman-Andrews, Lily
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Boycott KM
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