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Rapid Targeted Genomics in Critically Ill Newborns.

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Title: Rapid Targeted Genomics in Critically Ill Newborns.
Authors: van Diemen, Cleo C., Kerstjens-Frederikse, Wilhelmina S., Bergman, Klasien A., de Koning, Tom J., Sikkema-Raddatz, Birgit, van der Velde, Joeri K., Abbott, Kristin M., Herkert, Johanna C., Löhner, Katharina, Rump, Patrick, Meems-Veldhuis, Martine T., Neerincx, Pieter B. T., Jongbloed, Jan D. H., van Ravenswaaij-Arts, Conny M., Swertz, Morris A., Sinke, Richard J., van Langen, Irene M., Wijmenga, Cisca
Source: Pediatrics. Oct2017, Vol. 140 Issue 4, p40-40. 1p.
Subjects: Catastrophic illness, Intensive care units, Longitudinal method, Neonatal intensive care, Pediatrics, Genomics, Turnaround time, Sequence analysis, Children, Diagnosis
Abstract: BACKGROUND: Rapid diagnostic whole-genome sequencing has been explored in critically ill newborns, hoping to improve their clinical care and replace time-consuming and/or invasive diagnostic testing. A previous retrospective study in a research setting showed promising results with diagnoses in 57%, but patients were highly selected for known and likely Mendelian disorders. The aim of our prospective study was to assess the speed and yield of rapid targeted genomic diagnostics for clinical application. METHODS: We included 23 critically ill children younger than 12 months in ICUs over a period of 2 years. A quick diagnosis could not be made after routine clinical evaluation and diagnostics. Targeted analysis of 3426 known disease genes was performed by using whole-genome sequencing data. We measured diagnostic yield, turnaround times, and clinical consequences. RESULTS: A genetic diagnosis was obtained in 7 patients (30%), with a median turnaround time of 12 days (ranging from 5 to 23 days). We identified compound heterozygous mutations in the EPG5 gene (Vici syndrome), the RMND1 gene (combined oxidative phosphorylation deficiency-11), and the EIF2B5 gene (vanishing white matter), and homozygous mutations in the KLHL41 gene (nemaline myopathy), the GFER gene (progressive mitochondrial myopathy), and the GLB1 gene (GM1-gangliosidosis). In addition, a Ip36.33p36.32 microdeletion was detected in a child with cardiomyopathy. CONCLUSIONS: Rapid targeted genomics combined with copy number variant detection adds important value in the neonatal and pediatric intensive care setting. It led to a fast diagnosis in 30% of critically ill children for whom the routine clinical workup was unsuccessful. [ABSTRACT FROM AUTHOR]
Copyright of Pediatrics is the property of American Academy of Pediatrics and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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PubType: Academic Journal
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  Data: Rapid Targeted Genomics in Critically Ill Newborns.
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  Data: <searchLink fieldCode="AR" term="%22van+Diemen%2C+Cleo+C%2E%22">van Diemen, Cleo C.</searchLink><br /><searchLink fieldCode="AR" term="%22Kerstjens-Frederikse%2C+Wilhelmina+S%2E%22">Kerstjens-Frederikse, Wilhelmina S.</searchLink><br /><searchLink fieldCode="AR" term="%22Bergman%2C+Klasien+A%2E%22">Bergman, Klasien A.</searchLink><br /><searchLink fieldCode="AR" term="%22de+Koning%2C+Tom+J%2E%22">de Koning, Tom J.</searchLink><br /><searchLink fieldCode="AR" term="%22Sikkema-Raddatz%2C+Birgit%22">Sikkema-Raddatz, Birgit</searchLink><br /><searchLink fieldCode="AR" term="%22van+der+Velde%2C+Joeri+K%2E%22">van der Velde, Joeri K.</searchLink><br /><searchLink fieldCode="AR" term="%22Abbott%2C+Kristin+M%2E%22">Abbott, Kristin M.</searchLink><br /><searchLink fieldCode="AR" term="%22Herkert%2C+Johanna+C%2E%22">Herkert, Johanna C.</searchLink><br /><searchLink fieldCode="AR" term="%22Löhner%2C+Katharina%22">Löhner, Katharina</searchLink><br /><searchLink fieldCode="AR" term="%22Rump%2C+Patrick%22">Rump, Patrick</searchLink><br /><searchLink fieldCode="AR" term="%22Meems-Veldhuis%2C+Martine+T%2E%22">Meems-Veldhuis, Martine T.</searchLink><br /><searchLink fieldCode="AR" term="%22Neerincx%2C+Pieter+B%2E+T%2E%22">Neerincx, Pieter B. T.</searchLink><br /><searchLink fieldCode="AR" term="%22Jongbloed%2C+Jan+D%2E+H%2E%22">Jongbloed, Jan D. H.</searchLink><br /><searchLink fieldCode="AR" term="%22van+Ravenswaaij-Arts%2C+Conny+M%2E%22">van Ravenswaaij-Arts, Conny M.</searchLink><br /><searchLink fieldCode="AR" term="%22Swertz%2C+Morris+A%2E%22">Swertz, Morris A.</searchLink><br /><searchLink fieldCode="AR" term="%22Sinke%2C+Richard+J%2E%22">Sinke, Richard J.</searchLink><br /><searchLink fieldCode="AR" term="%22van+Langen%2C+Irene+M%2E%22">van Langen, Irene M.</searchLink><br /><searchLink fieldCode="AR" term="%22Wijmenga%2C+Cisca%22">Wijmenga, Cisca</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Pediatrics%22">Pediatrics</searchLink>. Oct2017, Vol. 140 Issue 4, p40-40. 1p.
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  Data: <searchLink fieldCode="DE" term="%22Catastrophic+illness%22">Catastrophic illness</searchLink><br /><searchLink fieldCode="DE" term="%22Intensive+care+units%22">Intensive care units</searchLink><br /><searchLink fieldCode="DE" term="%22Longitudinal+method%22">Longitudinal method</searchLink><br /><searchLink fieldCode="DE" term="%22Neonatal+intensive+care%22">Neonatal intensive care</searchLink><br /><searchLink fieldCode="DE" term="%22Pediatrics%22">Pediatrics</searchLink><br /><searchLink fieldCode="DE" term="%22Genomics%22">Genomics</searchLink><br /><searchLink fieldCode="DE" term="%22Turnaround+time%22">Turnaround time</searchLink><br /><searchLink fieldCode="DE" term="%22Sequence+analysis%22">Sequence analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Children%22">Children</searchLink><br /><searchLink fieldCode="DE" term="%22Diagnosis%22">Diagnosis</searchLink>
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  Label: Abstract
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  Data: BACKGROUND: Rapid diagnostic whole-genome sequencing has been explored in critically ill newborns, hoping to improve their clinical care and replace time-consuming and/or invasive diagnostic testing. A previous retrospective study in a research setting showed promising results with diagnoses in 57%, but patients were highly selected for known and likely Mendelian disorders. The aim of our prospective study was to assess the speed and yield of rapid targeted genomic diagnostics for clinical application. METHODS: We included 23 critically ill children younger than 12 months in ICUs over a period of 2 years. A quick diagnosis could not be made after routine clinical evaluation and diagnostics. Targeted analysis of 3426 known disease genes was performed by using whole-genome sequencing data. We measured diagnostic yield, turnaround times, and clinical consequences. RESULTS: A genetic diagnosis was obtained in 7 patients (30%), with a median turnaround time of 12 days (ranging from 5 to 23 days). We identified compound heterozygous mutations in the EPG5 gene (Vici syndrome), the RMND1 gene (combined oxidative phosphorylation deficiency-11), and the EIF2B5 gene (vanishing white matter), and homozygous mutations in the KLHL41 gene (nemaline myopathy), the GFER gene (progressive mitochondrial myopathy), and the GLB1 gene (GM1-gangliosidosis). In addition, a Ip36.33p36.32 microdeletion was detected in a child with cardiomyopathy. CONCLUSIONS: Rapid targeted genomics combined with copy number variant detection adds important value in the neonatal and pediatric intensive care setting. It led to a fast diagnosis in 30% of critically ill children for whom the routine clinical workup was unsuccessful. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Pediatrics is the property of American Academy of Pediatrics and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=125725479
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        Value: 10.1542/peds.2016-2854
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        Text: English
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      – SubjectFull: Longitudinal method
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      – SubjectFull: Sequence analysis
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      – SubjectFull: Children
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