Addressing ethical and laboratory challenges for initiation of a rapid whole genome sequencing program

J Clin Transl Sci. 2021 Aug 9;5(1):e177. doi: 10.1017/cts.2021.833. eCollection 2021. ABSTRACT Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research […]

Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency

Cold Spring Harb Mol Case Stud. 2021 Jun 11;7(3):a006091. doi: 10.1101/mcs.a006091. Print 2021 Jun. ABSTRACT Rapid whole-genome sequencing (rWGS) has shown that genetic diseases are a common cause of infant mortality in neonatal intensive care units. Dried blood spots collected for newborn screening allow investigation of causes of infant mortality that were not diagnosed during […]

Project Baby Bear: Rapid precision care incorporating rWGS in 5 California children’s hospitals demonstrates improved clinical outcomes and reduced costs of care

Am J Hum Genet. 2021 May 29:S0002-9297(21)00192-0. doi: 10.1016/j.ajhg.2021.05.008. Online ahead of print. ABSTRACT Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care units (ICUs). Rapid whole-genome sequencing (rWGS)-based rapid precision medicine (RPM) is an intervention that has demonstrated improved clinical outcomes and reduced costs of care. However, the feasibility […]

Implementing Rapid Whole Genome Sequencing in Critical Care: A Qualitative Study of Facilitators and Barriers to New Technology Adoption

J Pediatr. 2021 May 20:S0022-3476(21)00496-0. doi: 10.1016/j.jpeds.2021.05.045. Online ahead of print. ABSTRACT OBJECTIVE: To characterize the views of members of the multi-disciplinary team regarding the implementation of Rapid Whole Genome Sequencing (rWGS) as a first-tier test for critically ill children in diverse children’s hospital settings. STUDY DESIGN: Qualitative interviews informed by implementation science theory were […]

Expanding the genotypic spectrum of ACTG2-related visceral myopathy

Cold Spring Harb Mol Case Stud. 2021 Apr 21:mcs.a006085. doi: 10.1101/mcs.a006085. Online ahead of print. ABSTRACT Visceral myopathies (VMs) encompass a spectrum of disorders characterized by chronic disruption of gastrointestinal function, with or without urinary system involvement. Pathogenic missense variation in smooth muscle gamma-actin gene (ACTG2) is associated with autosomal dominant VM. Whole genome sequencing […]

Rapid whole genome sequencing impacts care and resource utilization in infants with congenital heart disease

NPJ Genom Med. 2021 Apr 22;6(1):29. doi: 10.1038/s41525-021-00192-x. ABSTRACT Congenital heart disease (CHD) is the most common congenital anomaly and a major cause of infant morbidity and mortality. While morbidity and mortality are highest in infants with underlying genetic conditions, molecular diagnoses are ascertained in only ~20% of cases using widely adopted genetic tests. Furthermore, […]

Diagnosis of cytomegalovirus infection from clinical whole genome sequencing

Sci Rep. 2020 Jul 3;10(1):11020. doi: 10.1038/s41598-020-67656-5. ABSTRACT Rapid whole genome sequencing (rWGS) of peripheral blood has been used to detect microbial DNA in acute infections. Cytomegalovirus (CMV) is a herpesvirus capable of causing severe disease in neonates and immunocompromised patients. We identified CMV in patients undergoing diagnostic rWGS by matching reads that did not […]

Mortality in a neonate with molybdenum cofactor deficiency illustrates the need for a comprehensive rapid precision medicine system

Cold Spring Harb Mol Case Stud. 2020 Feb 3;6(1):a004705. doi: 10.1101/mcs.a004705. Print 2020 Feb. ABSTRACT Neonatal encephalopathy with seizures is a presentation in which rapid whole-genome sequencing (rWGS) has shown clinical utility and improved outcomes. We report a neonate who presented on the third day of life with seizures refractory to antiepileptic medications and neurologic […]