Overview

Genomic methods can significantly contribute to all facets of precision medicine, from diagnosis to prevention, therapeutic intervention, and management of acute and chronic illnesses. DNA based methods are already having a considerable impact across healthcare in fields that include: public health, infectious disease monitoring, acute and chronic disease, pharmacogenomics, prenatal testing and diagnosis, and therapeutic development. In this proposal, investigators are focusing on the application of genomic methods in precision medicine - specifically on rapid whole-genome sequencing of parents and children (i.e. a trio) for the identification of diseases that have genetic components.

Goals Primary goal: is to provide safe rapid whole genome sequencing to Neonatal Intensive Care Unit/Pediatric Intensive Care Unit patients.

Secondary goals: 1) Although several groups globally are implementing rapid sequencing of rare disease, these are predominantly in the research space, with many unanswered questions regarding the best way to implement them into a national healthcare system. Each country and their healthcare systems are unique, and valuable knowledge will be gained by implementing this process within a New Zealand context. As part of this the study will measure the impact on the individuals and families.

2) to expand the research team's understanding of non-coding disease-causing variants and methylation changes that contribute to severe disease in early life.

Primary Aims

1. To incorporate long-read RNA sequencing data into the diagnostic rapid Whole Genome Sequencing pipeline to provide a direct measure of the functional outcome of the variants of clinical concern.
2. To measure the clinical utility of analysing non-coding variants in the diagnosis of critically ill children who do not have pathogenic, likely pathogenic, or variants of unknown significance for mendelian disorders.
3. To identify, in a real-world setting within the New Zealand health-care system, the clinical and economic effects of deploying rapid Whole Genome Sequencing-informed rapid precision medicine for critically ill children.

Eligibility

Inclusion Criteria:

• Acutely ill inpatient
• Admitted to NICU or PICU between April 2023 - March 2026
• Within 1 week of hospitalization or within 1 week of development of abnormal response to standard therapy for an underlying condition
• Suspected genetic condition, without a clear non-genetic aetiology

Exclusion Criteria:

• Patients whose clinical course is entirely explained by
• Isolated prematurity
• Isolated unconjugated hyperbilirubinemia
• Infection or sepsis with expected response to therapy
• A previously confirmed genetic diagnosis that explains the clinical condition -
• Isolated transient neonatal tachypnoea
• Meconium aspiration syndrome
• Trauma
• Inability to source blood and buccal samples for DNA extraction from at least the mother and child