NICUSeq: A Trial to Evaluate the Clinical Utility of Human Whole Genome Sequencing (WGS) Compared to Standard of Care in Acute Care Neonates and Infants

This is a prospective, multi-site, randomized study to evaluate the clinical utility of cWGS
in each proband. Throughout this study, each proband will receive SOC testing as determined
by the site clinical team. Upon enrollment in the study, each proband will be randomly
assigned to the 15 day cWGS group or the SOC group. SOC is defined as the management of the
proband's care under the same or similar conditions as if the proband was not enrolled in
this study. A blood sample from each enrolled proband will be collected and shipped to the
Illumina Clinical Services Laboratory ("ICSL"), which is Clinical Laboratory Improvement
Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited. ICSL will
conduct cWGS testing with the TruGenome Undiagnosed Disease Test ("TruGenome Test"). The
TruGenome Test cWGS results will be provided to the Principal Investigator (PI) or designee
who will evaluate each proband test outcome based on the aggregate medical information,
informed by the cWGS or SOC results.

Proband Inclusion Criteria

1. Current admission in a Neonatal Intensive Care Unit/Intensive Care Unit at a
participating clinical site at the time of enrollment from day of life 0 to 120 days

2. A suspected genetic etiology of disease, based on objective clinical findings or other
phenotypic defects for which a genetic test would be considered

3. Must be able to have 1 - 1.25 ml tube of whole blood drawn for testing

4. One parent of the proband must be able to provide written informed consent

5. At least one biological parent must agree to participate and provide at least 4 ml of
whole blood for testing

Exclusion Criteria:

Proband Exclusion Criteria

1. Known non-genetic cause(s) of disease, disorder, or phenotypic defect

2. The phenotype is fully explained by complications of prematurity

3. Trisomy 13, 18 or 21 or Turner Syndrome is the likely diagnosis; such a proband will
be eligible if a diagnostic karyotype is normal

4. Blood transfusion within 48 hours (each proband will be re-eligible 48 hours after the
most recent transfusion)

5. The PI decides that the study is not in the best interest of the proband (for example,
the neonate or infant is at a high risk of severe morbidity or mortality within the
next 7 days and these risks could be mitigated by alternative testing). Subsequent
eligibility for enrollment of each proband is at the discretion of the site PI.