2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A single institution analysis of in-house whole genome sequencing within pediatric and neonatal intensive care units (The PISCES Study)

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The PISCES study examined the use of in-house whole genome sequencing (WGS) in pediatric and neonatal intensive care units (NICUs) compared to standard genetic testing utilizing external laboratories. The study enrolled patients under 1 year of age with suspected genetic disorders. Patients underwent both standard of care (SOC) testing and WGS. The diagnostic yield was analyzed, and turnaround time (TAT) was compared between WGS and clinical whole exome sequencing (WES).<br /><br />Among the 41 patients who completed the study, 12 (29%) were identified with genetic diagnoses that fully or partially explained their phenotype through the WGS analysis. Most of these patients (82%) had already been identified through SOC genetic testing. Only one patient (8%) had a diagnosis found exclusively through WGS. The TAT for WGS was significantly shorter than clinical WES (24.8 vs 49.3 days), but similar to targeted gene panel directed analysis (24.8 vs 21.0 days).<br /><br />The study used a panel of 1722 genes likely to cause genetic disorders in infancy, which captured most of the genetic diagnoses found in the study. However, 22q11.2 deletion syndrome was diagnosed through chromosomal microarray, not through the gene panel.<br /><br />Overall, in-house WGS provided similar diagnostic rates to SOC genetic testing and had a faster turnaround time compared to clinical WES. Further analysis is being conducted to evaluate the overall clinical utility and cost effectiveness of WGS implementation. The 1722 gene panel may provide an effective first-pass diagnostic analysis when full WGS analysis is not available. The study also presented specific diagnoses made through the PISCES WGS analysis, including Noonan syndrome, craniosynostosis, hereditary lymphedema, and others.<br /><br />In conclusion, the PISCES study demonstrates the benefits of in-house WGS for diagnosing complex infant and neonate cases in the ICU. WGS showed comparable diagnostic rates and turnaround time to current clinical tests. The study suggests that in-house WGS could be a valuable tool in clinical practice, offering faster and more comprehensive genetic testing for patients in intensive care.

Asset Subtitle

Submitter Only - Peter J. Nelson, BS; Presenting Author - Peter J. Nelson, BS; Co-Author - Cate Walsh Vockley, MS; Co-Author - Georgianne L. Arnold, MD; Co-Author - Jirair K. Bedoyan, MD, PhD, FACMG; Co-Author - Amina Kunovac, PhD; Co-Author - Lindsey Kelly, PhD; Co-Author - Dara Kozak, BS; Co-Author - Alexander N. Yatsenko, MD PhD; Co-Author - Jennifer M. Atkinson, PhD; Co-Author - Adrian V. Lee, PhD; Co-Author - Daniel B. Bellissimo, PhD; Co-Author - Jerry Vockley, MD, PhD, FACMG; Co-Author - Lina Ghaloul-Gonzalez, MD;

Meta Tag

Exome sequencing

Genetic Testing

Genome sequencing

Sequencing

Co-Author Cate Walsh Vockley, MS

Co-Author Georgianne L. Arnold, MD

Co-Author Jirair K. Bedoyan, MD, PhD, FACMG

Co-Author Amina Kunovac, PhD

Co-Author Lindsey Kelly, PhD

Co-Author Dara Kozak, BS

Co-Author Alexander N. Yatsenko, MD PhD

Co-Author Jennifer M. Atkinson, PhD

Co-Author Adrian V. Lee, PhD

Co-Author Daniel B. Bellissimo, PhD

Co-Author Jerry Vockley, MD, PhD, FACMG

Co-Author Lina Ghaloul-Gonzalez, MD

Presenting Author Peter J. Nelson, BS

Submitter Only Peter J. Nelson, BS

Keywords

PISCES study

in-house whole genome sequencing

pediatric

neonatal intensive care units

standard genetic testing

diagnostic yield

turnaround time

clinical whole exome sequencing

genetic diagnoses

gene panel