Clinical validity of phenotype-driven analysis software PhenoVar as a diagnostic aid for clinical geneticists in the interpretation of whole-exome sequencing data
Clinical validity of phenotype-driven analysis software PhenoVar as a diagnostic aid for clinical geneticists in the interpretation of whole-exome sequencing data
复制标题
表型驱动分析软件 PhenoVar 作为临床遗传学家解释全外显子组测序数据的诊断辅助工具的临床有效性
DOI：
10.1038/gim.2017.239
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发表时间：
2018
影响因子：
8.8
通讯作者：
S. Lévesque
中科院分区：
文献类型：
--
作者：
Fanny Thuriot;Caroline Buote;Elaine Gravel;S. Chénier;V. Désilets;B. Maranda;P. Waters;P. Jacques;S. Lévesque
PurposeWe试图确定全外显子组测序（WES）结合表型驱动的变异分析在疑似geneticdisorders.MethodsWES患者的诊断率进行了一个队列的51例畸形或不神经发育障碍的病因不明。对于每例患者，临床遗传学家审查了表型，并使用表型驱动的分析软件PhenoVar（http：//phenovar.med.usherbrooke.ca/）分析WES变体。返回的潜在诊断的优先列表由临床遗传学家审查，临床遗传学家选择待通过分离分析确认的候选变体。平行进行单个变体的常规分析。由此产生的候选变异随后由同一遗传学家审查，以确定任何额外的潜在diagnosis.ResultsA分子诊断确定在35%的患者使用常规分析，和17这18个诊断独立确定使用PhenoVar。当省略可选的“最小表型截止值”过滤器时，PhenoVar最初遗漏的唯一诊断被挽救。PhenoVar减少了一半的潜在诊断每名患者的数量相比，传统的analysis.ConclusionPhenotype-driven软件优先WES变体，提供了一个有效的诊断援助，临床遗传学家和实验室，并应纳入临床实践。
PurposeWe sought to determine the diagnostic yield of whole-exome sequencing (WES) combined with phenotype-driven analysis of variants in patients with suspected genetic disorders.MethodsWES was performed on a cohort of 51 patients presenting dysmorphisms with or without neurodevelopmental disorders of undetermined etiology. For each patient, a clinical geneticist reviewed the phenotypes and used the phenotype-driven analysis software PhenoVar (http://phenovar.med.usherbrooke.ca/) to analyze WES variants. The prioritized list of potential diagnoses returned was reviewed by the clinical geneticist, who selected candidate variants to be confirmed by segregation analysis. Conventional analysis of the individual variants was performed in parallel. The resulting candidate variants were subsequently reviewed by the same geneticist, to identify any additional potential diagnoses.ResultsA molecular diagnosis was identified in 35% of the patients using the conventional analysis, and 17 of these 18 diagnoses were independently identified using PhenoVar. The only diagnosis initially missed by PhenoVar was rescued when the optional “minimal phenotypic cutoff” filter was omitted. PhenoVar reduced by half the number of potential diagnoses per patient compared with the conventional analysis.ConclusionPhenotype-driven software prioritizes WES variants, provides an efficient diagnostic aid to clinical geneticists and laboratories, and should be incorporated in clinical practice.
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影响因子：
7
作者：
Cooper, GM;Stone, EA;Sidow, A
通讯作者：
Sidow, A
影响因子：
120.7
作者：
Yang, Yaping;Muzny, Donna M.;Xia, Fan;Niu, Zhiyv;Person, Richard;Ding, Yan;Ward, Patricia;Braxton, Alicia;Wang, Min;Buhay, Christian;Veeraraghavan, Narayanan;Hawes, Alicia;Chiang, Theodore;Leduc, Magalie;Beuten, Joke;Zhang, Jing;He, Weimin;Scull, Jennifer;Willis, Alecia;Landsverk, Megan;Craigen, William J.;Bekheirnia, Mir Reza;Stray-Pedersen, Asbjorg;Liu, Pengfei;Wen, Shu;Alcaraz, Wendy;Cui, Hong;Walkiewicz, Magdalena;Reid, Jeffrey;Bainbridge, Matthew;Patel, Ankita;Boerwinkle, Eric;Beaudet, Arthur L.;Lupski, James R.;Plon, Sharon E.;Gibbs, Richard A.;Eng, Christine M.
通讯作者：
Eng, Christine M.
影响因子：
7
作者：
Robinson PN;Köhler S;Oellrich A;Sanger Mouse Genetics Project;Wang K;Mungall CJ;Lewis SE;Washington N;Bauer S;Seelow D;Krawitz P;Gilissen C;Haendel M;Smedley D
通讯作者：
Smedley D
影响因子：
9.8
作者：
Singleton, Marc V.;Guthery, Stephen L.;Yandell, Mark
通讯作者：
Yandell, Mark