Rapid Nephrogenomics in Intensive Care for Early Intervention in Adult Thrombotic Microangiopathies
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Le résumé fourni par la source
Background: Nephrogenomics, represents the study of genetic factors influencing kidney function and diseases. The field has rapidly advanced in recent years due to the development of high-throughput sequencing technologies such as next-generation sequencing (NGS). Thrombotic microangiopathy (TMA) encompasses various genetically driven diseases with some of them could benefit from early intervention (C5 blocking, VitB12 therapy). Structural variants (SV) in the CFH/CFHR gene region leading to the formation of gene fusions constitute a specific molecular diagnostic bottleneck associated with 5% of complement dependent TMA (c-TMA) cases. However, the highly repetitive character of sequences in this region, makes it difficult to detect these SVs when using standard short-read sequencing. Our current turn-around time for the diagnosis of TMA (3 weeks) is too long in some clinical context. Ultra-fast sequencing techniques using long reads Nanopores technologies can provide efficient and versatile cost-effective analysis in a matter of hours. Methods: Here we report diagnostic results of Nanopore sequencing with adaptive sampling in TMA, which is a method to enrich sequences or genes of interest. We lower our TAT to 5 days with long reads sequencing and adaptive sampling. We established a rapid molecular diagnosis that allows time-decision making on the use of anti-C5 treatment for complement-mediated TMA (c-TMA), as averting unnecessary costly and potentially harmful therapy in patients who will in any case not respond to the anti-C5 treatment. Results: With rapid and long reads sequencing, we were able to diagnosis a case of independent complement-TMA with a variant in MMACHC. We also retrospectively validated the detection of known SVs in four samples on which MLPA (Gold standard method to identify SV) analysis was performed. We were able to detect all the SVs in these samples such as CFH-CFHR1 hybrid, CFHR1-CFH hybrids of different sizes and a deletion of CFHR1-CFHR3. Conclusions: Thus, rapid genomics using nanopore technologies can provide valuable insights into disease detection and treatment efficacy improving patient diagnosis and prognostic, enabling optimal and early therapeutic intervention. Funding: Government Support - Non-U.S.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Rapid Nephrogenomics in Intensive Care for Early Intervention in Adult Thrombotic Microangiopathies
- Date Crossref
- 01/11/2023
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Inserm pays non établi dans la noticeOrganisme public
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Sorbonne Université pays non établi dans la noticeUniversité ou école supérieure
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Assistance Publique – Hôpitaux de Paris pays non établi dans la noticeÉtablissement de santé
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Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée pays non établi dans la noticeStructure de recherche
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Quantum Genomics (France) pays non établi dans la noticeEntreprise
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Institut Curie pays non établi dans la noticeOrganisation à but non lucratif
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Hôpital Européen Georges-Pompidou pays non établi dans la noticeÉtablissement de santé
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Hôpital Européen pays non établi dans la noticeÉtablissement de santé
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CNR-MAT APHP pays non établi dans la noticeInstitution
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SeqOne Genomics pays non établi dans la noticeInstitution
Inserm, Sorbonne Université et Assistance Publique – Hôpitaux de Paris, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.