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Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours

Rapid Whole Genome Sequencing (rWGS) represents a valuable exploration in critically ill pediatric patients. Early diagnosis allows care to be adjusted. We evaluated the feasibility, turnaround time (TAT), yield, and utility of rWGS in Belgium. Twenty-one unrelated critically ill patients were recru...

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Autores principales: Lumaka, Aimé, Fasquelle, Corinne, Debray, Francois-Guillaume, Alkan, Serpil, Jacquinet, Adeline, Harvengt, Julie, Boemer, François, Mulder, André, Vaessen, Sandrine, Viellevoye, Renaud, Palmeira, Leonor, Charloteaux, Benoit, Brysse, Anne, Bulk, Saskia, Rigo, Vincent, Bours, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967120/
https://www.ncbi.nlm.nih.gov/pubmed/36835410
http://dx.doi.org/10.3390/ijms24044003
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author Lumaka, Aimé
Fasquelle, Corinne
Debray, Francois-Guillaume
Alkan, Serpil
Jacquinet, Adeline
Harvengt, Julie
Boemer, François
Mulder, André
Vaessen, Sandrine
Viellevoye, Renaud
Palmeira, Leonor
Charloteaux, Benoit
Brysse, Anne
Bulk, Saskia
Rigo, Vincent
Bours, Vincent
author_facet Lumaka, Aimé
Fasquelle, Corinne
Debray, Francois-Guillaume
Alkan, Serpil
Jacquinet, Adeline
Harvengt, Julie
Boemer, François
Mulder, André
Vaessen, Sandrine
Viellevoye, Renaud
Palmeira, Leonor
Charloteaux, Benoit
Brysse, Anne
Bulk, Saskia
Rigo, Vincent
Bours, Vincent
author_sort Lumaka, Aimé
collection PubMed
description Rapid Whole Genome Sequencing (rWGS) represents a valuable exploration in critically ill pediatric patients. Early diagnosis allows care to be adjusted. We evaluated the feasibility, turnaround time (TAT), yield, and utility of rWGS in Belgium. Twenty-one unrelated critically ill patients were recruited from the neonatal intensive care units, the pediatric intensive care unit, and the neuropediatric unit, and offered rWGS as a first tier test. Libraries were prepared in the laboratory of human genetics of the University of Liège using Illumina DNA PCR-free protocol. Sequencing was performed on a NovaSeq 6000 in trio for 19 and in duo for two probands. The TAT was calculated from the sample reception to the validation of results. Clinical utility data were provided by treating physicians. A definite diagnosis was reached in twelve (57.5%) patients in 39.80 h on average (range: 37.05–43.7). An unsuspected diagnosis was identified in seven patients. rWGS guided care adjustments in diagnosed patients, including a gene therapy, an off-label drug trial and two condition-specific treatments. We successfully implemented the fastest rWGS platform in Europe and obtained one of the highest rWGS yields. This study establishes the path for a nationwide semi-centered rWGS network in Belgium.
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spelling pubmed-99671202023-02-26 Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours Lumaka, Aimé Fasquelle, Corinne Debray, Francois-Guillaume Alkan, Serpil Jacquinet, Adeline Harvengt, Julie Boemer, François Mulder, André Vaessen, Sandrine Viellevoye, Renaud Palmeira, Leonor Charloteaux, Benoit Brysse, Anne Bulk, Saskia Rigo, Vincent Bours, Vincent Int J Mol Sci Article Rapid Whole Genome Sequencing (rWGS) represents a valuable exploration in critically ill pediatric patients. Early diagnosis allows care to be adjusted. We evaluated the feasibility, turnaround time (TAT), yield, and utility of rWGS in Belgium. Twenty-one unrelated critically ill patients were recruited from the neonatal intensive care units, the pediatric intensive care unit, and the neuropediatric unit, and offered rWGS as a first tier test. Libraries were prepared in the laboratory of human genetics of the University of Liège using Illumina DNA PCR-free protocol. Sequencing was performed on a NovaSeq 6000 in trio for 19 and in duo for two probands. The TAT was calculated from the sample reception to the validation of results. Clinical utility data were provided by treating physicians. A definite diagnosis was reached in twelve (57.5%) patients in 39.80 h on average (range: 37.05–43.7). An unsuspected diagnosis was identified in seven patients. rWGS guided care adjustments in diagnosed patients, including a gene therapy, an off-label drug trial and two condition-specific treatments. We successfully implemented the fastest rWGS platform in Europe and obtained one of the highest rWGS yields. This study establishes the path for a nationwide semi-centered rWGS network in Belgium. MDPI 2023-02-16 /pmc/articles/PMC9967120/ /pubmed/36835410 http://dx.doi.org/10.3390/ijms24044003 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lumaka, Aimé
Fasquelle, Corinne
Debray, Francois-Guillaume
Alkan, Serpil
Jacquinet, Adeline
Harvengt, Julie
Boemer, François
Mulder, André
Vaessen, Sandrine
Viellevoye, Renaud
Palmeira, Leonor
Charloteaux, Benoit
Brysse, Anne
Bulk, Saskia
Rigo, Vincent
Bours, Vincent
Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours
title Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours
title_full Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours
title_fullStr Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours
title_full_unstemmed Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours
title_short Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours
title_sort rapid whole genome sequencing diagnoses and guides treatment in critically ill children in belgium in less than 40 hours
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967120/
https://www.ncbi.nlm.nih.gov/pubmed/36835410
http://dx.doi.org/10.3390/ijms24044003
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