Rapid whole genome sequencing of critically ill pediatric patients from genetically underrepresented populations

Genome Med. 2022 May 24;14(1):56. doi: 10.1186/s13073-022-01061-7.

Abstract

We describe a case series of five infants (age range: 1-90 days; 4 females and 1 male) who presented to Al Jalila Children's intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or Pakistani. Trio rapid whole genome sequencing (rWGS) was performed on all five patients and their parents within the hospital's genomics facility. Results were returned within ~37 h from blood sample draws and were diagnostic in 3 out of 5 patients. Positive findings were a homozygous pathogenic variant in POMT1 gene causing muscular dystrophydystroglycanopathy, a mosaic tetrasomy of the short arm of chromosome 12 (12p13.33p11.1) causing Pallister-Killian syndrome, and compound heterozygous pathogenic variants in the LIPA gene causing lysosomal acid lipase deficiency and Wolman disease. The rWGS analysis provided fast and precise diagnostic findings in those 3 patients and also aided in devising better management plans for them in the intensive care setting. For example, the 3-month-old infant with pathogenic variants in the LIPA gene is now a candidate for an FDA-approved, potentially lifesaving enzyme replacement therapy (sebelipase alfa). Our case series emphasize the feasibility and utility of rWGS in pediatric intensive care setting, in a diverse population that has long been underserved in genomic services. Significant investments in local healthcare infrastructure are needed, globally, for more equitable access of genomic medicine among vulnerable patients.

Publication types

  • Case Reports
  • Letter

MeSH terms

  • Chromosome Disorders
  • Chromosomes, Human, Pair 12
  • Critical Illness* / therapy
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Whole Genome Sequencing* / methods
  • Wolman Disease

Supplementary concepts

  • Pallister Killian syndrome