دورية أكاديمية
Stepwise use of genomics and transcriptomics technologies increases diagnostic yield in Mendelian disorders
| العنوان: | Stepwise use of genomics and transcriptomics technologies increases diagnostic yield in Mendelian disorders |
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| المؤلفون: | Estelle Colin, Yannis Duffourd, Martin Chevarin, Emilie Tisserant, Simon Verdez, Julien Paccaud, Ange-Line Bruel, Frédéric Tran Mau-Them, Anne-Sophie Denommé-Pichon, Julien Thevenon, Hana Safraou, Thomas Besnard, Alice Goldenberg, Benjamin Cogné, Bertrand Isidor, Julian Delanne, Arthur Sorlin, Sébastien Moutton, Mélanie Fradin, Christèle Dubourg, Magali Gorce, Dominique Bonneau, Salima El Chehadeh, François-Guillaume Debray, Martine Doco-Fenzy, Kevin Uguen, Nicolas Chatron, Bernard Aral, Nathalie Marle, Paul Kuentz, Anne Boland, Robert Olaso, Jean-François Deleuze, Damien Sanlaville, Patrick Callier, Christophe Philippe, Christel Thauvin-Robinet, Laurence Faivre, Antonio Vitobello |
| المصدر: | Frontiers in Cell and Developmental Biology, Vol 11 (2023) |
| بيانات النشر: | Frontiers Media S.A. |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | genome sequencing, RNA-seq, optical genome mapping, long-read sequencing, clinical diagnoses, Biology (General), QH301-705.5 |
| الوصف: | Purpose: Multi-omics offer worthwhile and increasingly accessible technologies to diagnostic laboratories seeking potential second-tier strategies to help patients with unresolved rare diseases, especially patients clinically diagnosed with a rare OMIM (Online Mendelian Inheritance in Man) disease. However, no consensus exists regarding the optimal diagnostic care pathway to adopt after negative results with standard approaches.Methods: In 15 unsolved individuals clinically diagnosed with recognizable OMIM diseases but with negative or inconclusive first-line genetic results, we explored the utility of a multi-step approach using several novel omics technologies to establish a molecular diagnosis. Inclusion criteria included a clinical autosomal recessive disease diagnosis and single heterozygous pathogenic variant in the gene of interest identified by first-line analysis (60%–9/15) or a clinical diagnosis of an X-linked recessive or autosomal dominant disease with no causative variant identified (40%–6/15). We performed a multi-step analysis involving short-read genome sequencing (srGS) and complementary approaches such as mRNA sequencing (mRNA-seq), long-read genome sequencing (lrG), or optical genome mapping (oGM) selected according to the outcome of the GS analysis.Results: SrGS alone or in combination with additional genomic and/or transcriptomic technologies allowed us to resolve 87% of individuals by identifying single nucleotide variants/indels missed by first-line targeted tests, identifying variants affecting transcription, or structural variants sometimes requiring lrGS or oGM for their characterization.Conclusion: Hypothesis-driven implementation of combined omics technologies is particularly effective in identifying molecular etiologies. In this study, we detail our experience of the implementation of genomics and transcriptomics technologies in a pilot cohort of previously investigated patients with a typical clinical diagnosis without molecular etiology. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2296-634X |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1021920/fullTest; https://doaj.org/toc/2296-634XTest; https://doaj.org/article/4593e6258ee746c78872071719392347Test |
| DOI: | 10.3389/fcell.2023.1021920 |
| الإتاحة: | https://doi.org/10.3389/fcell.2023.1021920Test https://doaj.org/article/4593e6258ee746c78872071719392347Test |
| رقم الانضمام: | edsbas.5F9E9750 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2296634X |
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| DOI: | 10.3389/fcell.2023.1021920 |