Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders

Smith, Laurie D.; Willig, Laurel K.; Kingsmore, Stephen F.

doi:10.1101/cshperspect.a023168

Cited by 89 publications

(79 citation statements)

References 79 publications

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“…A recent flurry of studies demonstrates the utility and increased use of WES/WGS, especially rapid WES/WGS, for critically ill patients in neonatal and pediatric intensive care unit (ICU) settings (Meng et al, 2017;Petrikin et al, 2018;Petrikin, Willig, Smith, & Kingsmore, 2015;Smith, Willig, & Kingsmore, 2016;Stark et al, 2016). They show broad genetic testing like WES/WGS has meaningful potential to impact care decisions, spanning from identifying treatment of the underlying disease to withdrawing support for incurable disorders.…”

Section: Introductionmentioning

confidence: 99%

Factors complicating the informed consent process for whole exome sequencing in neonatal and pediatic intensive care units

Diamonstein¹

2019

Journal of Genetic Counseling

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Whole exome and whole genome sequencing (WES/WGS) is increasingly utilized in inpatient settings such as neonatal and pediatric intensive care units (ICU), but no research has explored the process of informed consent in this setting. My experience as an inpatient genetic counselor has illuminated factors unique to the ICU that may threaten elements of informed consent such as voluntariness, disclosure, understanding, and capacity. I present three cases that exemplify elements complicating consent counseling for WES/WGS in the ICU, including the emotional state of the parents, involvements of other healthcare providers, environmental distractions and competing clinical priorities. I offer strategies to navigate these factors based on my experience.

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Section: Introductionmentioning

confidence: 99%

Factors complicating the informed consent process for whole exome sequencing in neonatal and pediatic intensive care units

Diamonstein¹

2019

Journal of Genetic Counseling

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“…7,10 The need for a rapid comprehensive genetic diagnosis in ICUs for critically ill babies, especially those in level III and IV NICUs is paramount for both prognostication and clinical decision-making. 8,16 …”

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confidence: 99%

Use of Exome Sequencing for Infants in Intensive Care Units

et al. 2017

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Importance: While congenital malformations and genetic diseases are a leading cause of early infant death, the contribution of single-gene disorders in this group is undetermined. Objective: To determine the diagnostic yield and utility of clinical exome sequencing in critically ill infants. Design, setting, participants: Clinical exome sequencing was performed on 278 unrelated infants within the first 100 days of life, admitted to Texas Children’s Hospital in Houston, over a period of five years, between December 2011 and January 2017. Exome sequencing types included proband exome, trio exome, and critical trio exome, a rapid genomic assay for seriously-ill infants. Main outcomes and measures: Indications for testing, diagnostic yield of clinical exome sequencing, turnaround time, molecular findings, patient age at diagnosis, and impact on medical management in a group of critically ill infants suspected to have genetic disorders. Results: Clinical indications for exome sequencing included a wide range of medical concerns. Overall, molecular diagnosis was achieved in 102/278 infants by clinical exome sequencing with a diagnostic yield of 36.7%. The diagnosis affected medical management in 53/102 (52.0%) of infants, with substantial impact on informed redirection of care, initiation of new subspecialist care, medication/dietary modifications, and furthering life-saving procedures in select patients. Critical trio exome revealed a molecular diagnosis in 32/63 infants (50.8%) at 33.1±5.6 days of life with turnaround time (TAT) of 13.0 ± 0.4 days. Clinical care was altered by the diagnosis in 23/32 (71.9%) patients. The diagnostic yield, patient age at diagnosis, and medical impact in the group that underwent critical trio exome is significantly different comparing to regular exome testing. For deceased infants (n=81), genetic disorders were molecular diagnosed in 39 (48.1%) by exome sequencing with implications for recurrence risk counseling. Conclusions and relevance: Exome sequencing is a powerful tool for the diagnostic evaluation of critically ill infants with suspected monogenic disorders in the neonatal and pediatric ICUs, leading to notable impact on clinical decision-making.

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“…Several hyperammonemia gene panels are commercially available, but results take several weeks. With rapid next‐generation sequencing (NGS) currently approaching 48 hr turnaround, potential for timely molecular screening will be increasingly possible …”

Section: Discussionmentioning

confidence: 99%

Pegylated asparaginase as cause of fatal hyperammonemia in patients with latent urea cycle disorder

Peters

Zee-Cheng

Kuhl

et al. 2018

Pediatric Blood & Cancer

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Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders

Cited by 89 publications

References 79 publications

Factors complicating the informed consent process for whole exome sequencing in neonatal and pediatic intensive care units

Factors complicating the informed consent process for whole exome sequencing in neonatal and pediatic intensive care units

Use of Exome Sequencing for Infants in Intensive Care Units

Pegylated asparaginase as cause of fatal hyperammonemia in patients with latent urea cycle disorder

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