RAPIDOMICS: rapid genome-wide sequencing in a neonatal intensive care unit—successes and challenges
| Autor: | Suzanne M E Lewis, Leah Tooman, Horacio Osiovich, Margot I. Van Allen, Linlea Armstrong, Harinder Gill, Jan M. Friedman, Jan Christilaw, Millan S. Patel, Ilaria Guella, Lorne A. Clarke, Matthew J. Farrer, Tara Candido, Anna Lehman, Anne Synnes, Alfonso Solimano, Daniel M. Evans, Joseph Ting, Margaret L. McKinnon, Christèle du Souich, William T. Gibson, Sarah M. Nikkel, Alison M. Elliott, Pascal M. Lavoie |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Neonatal intensive care unit Critical Illness Genetic counseling Clinical Decision-Making Genetic Counseling Pilot Projects Genome 03 medical and health sciences Health services 0302 clinical medicine Intensive Care Units Neonatal 030225 pediatrics Intensive care Outcome Assessment Health Care Exome Sequencing Humans Medicine Genetic Testing 030212 general & internal medicine Exome sequencing business.industry Patient Selection Genetic Diseases Inborn Infant Newborn Microarray Analysis Infant mortality Preliminary diagnosis Pediatrics Perinatology and Child Health Intensive Care Neonatal Female business |
| Zdroj: | European Journal of Pediatrics. 178:1207-1218 |
| ISSN: | 1432-1076 0340-6199 |
| DOI: | 10.1007/s00431-019-03399-4 |
| Popis: | Genetic disorders are one of the leading causes of infant mortality and are frequent in neonatal intensive care units (NICUs). Rapid genome-wide sequencing (GWS; whole genome or exome sequencing (ES)), due to its diagnostic capabilities and immediate impacts on medical management, is becoming an appealing testing option in the NICU setting. RAPIDOMICS was a trio-based rapid ES pilot study of 25 babies with suspected genetic disorders in the BC Women's Hospital NICU. ES and bioinformatic analysis were performed after careful patient ascertainment. Trio analysis was performed using an in-house pipeline reporting variants in known disease-causing genes. Variants interpreted by the research team as definitely or possibly causal of the infant's phenotype were Sanger validated in a clinical laboratory. The average time to preliminary diagnosis was 7.2 days. Sanger validation was pursued in 15 patients for 13 autosomal dominant and 2 autosomal recessive disorders, with an overall diagnostic rate (partial or complete) of 60%.Conclusion: In total, 72% of patients enrolled had a genomic diagnosis achieved through ES, multi-gene panel testing or chromosomal microarray analysis. Among these, there was an 83% rate of significant and immediate impact on medical decision-making directly related to new knowledge of the diagnosis. Health service implementation challenges and successes are discussed. What is Known: • Rapid genome-wide sequencing in the neonatal intensive care setting has a greater diagnostic hit rate and impact on medical management than conventional genetic testing. However, the impact of consultation with genetics and patient ascertainment requires further investigation. What is New: • This study demonstrates the importance of genetic consultation and careful patient selection prior to pursuing exome sequencing (ES). • In total, 15/25 (60%) patients achieved a diagnosis through ES and 18/25 (72%) through ES, multi-gene panel testing or chromosomal microarray analysis with 83% of those having immediate effects on medical management. |
| Databáze: | OpenAIRE |
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