对来自未解决罕见病病例的 ES 数据中的 CNV 进行全面的重新分析,从而得出新的诊断结果。

IF 4.7 2区 医学 Q1 GENETICS & HEREDITY NPJ Genomic Medicine Pub Date : 2024-10-26 DOI:10.1038/s41525-024-00436-6
German Demidov, Burcu Yaldiz, José Garcia-Pelaez, Elke de Boer, Nika Schuermans, Liedewei Van de Vondel, Ida Paramonov, Lennart F Johansson, Francesco Musacchia, Elisa Benetti, Gemma Bullich, Karolis Sablauskas, Sergi Beltran, Christian Gilissen, Alexander Hoischen, Stephan Ossowski, Richarda de Voer, Katja Lohmann, Carla Oliveira, Ana Topf, Lisenka E L M Vissers, Steven Laurie
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引用次数: 0

摘要

我们报告了对来自 5757 个罕见病(RD)家庭的 9171 个外显子测序数据集进行拷贝数变异(CNV)再分析的结果。重新分析的数据差异极大,它们是由欧洲 42 个不同的研究小组在 Solve-RD 项目中合作使用 28 种不同的富集试剂盒生成的。每个研究小组之前都对数据进行了自己的分析,但都未能发现致病变异。我们采用了三种 CNV 调用算法,以最大限度地提高灵敏度,并将四个欧洲参考网络合作伙伴提供的与相关基因重叠的罕见 CNV 移交给临床专家进行解读。通过重新分析,我们为样本中的 51 个家庭提供了分子诊断,其中 ClinCNV 在三种算法中表现最佳。我们还在另外 34 个个体中发现了部分可解释的致病 CNV。这项工作说明了重新分析 ES 冷病例 CNV 的价值。
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Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses.

We report the results of a comprehensive copy number variant (CNV) reanalysis of 9171 exome sequencing datasets from 5757 families affected by a rare disease (RD). The data reanalysed was extremely heterogeneous, having been generated using 28 different enrichment kits by 42 different research groups across Europe partnering in the Solve-RD project. Each research group had previously undertaken their own analysis of the data but failed to identify disease-causing variants. We applied three CNV calling algorithms to maximise sensitivity, and rare CNVs overlapping genes of interest, provided by four partner European Reference Networks, were taken forward for interpretation by clinical experts. This reanalysis has resulted in a molecular diagnosis being provided to 51 families in this sample, with ClinCNV performing the best of the three algorithms. We also identified partially explanatory pathogenic CNVs in a further 34 individuals. This work illustrates the value of reanalysing ES cold cases for CNVs.

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来源期刊
NPJ Genomic Medicine
NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
1.90%
发文量
67
审稿时长
17 weeks
期刊介绍: npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.
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