North Carolina Newborn Exome Sequencing for Universal Screening

The investigators will enroll and perform whole exome sequencing on two cohorts of patients. One cohort will consist of two hundred newborns with no known conditions whose parents will be recruited during the mother's pregnancy. The second cohort will include two hundred infants and children up to the age of five years with diagnosed conditions including conditions detected through standard newborn screening such as phenylketonuria and other inborn errors of metabolism, hearing loss and other rare conditions that may fit criteria for newborn screening in the future.

Parents will be introduced to the study by their clinician or a study recruiter. Those who agree to enroll in Phase I will review an online decision guide and be offered a study visit conducted by a genetic counselor to obtain informed consent for genomic sequencing of their child. Parents consenting to have their child's genome sequenced will be seen after the child's birth or at a convenient pre-arranged time and duplicate saliva samples will be collected from the children and one sample will be sent to the BioSpecimen Processing (BSP) Facility and to Dr. Jonathan Berg's laboratory for sequencing and the other sent to the Molecular Genetics Laboratory (MGL) for DNA extraction and storage until needed for clinical confirmation. Results will be returned for diagnostic (in the Diagnosed cohort) and medically actionable disorders of childhood (both cohorts). Two-thirds of parents who consent to sequencing will be randomly assigned to be eligible to request additional findings and use a supplement of the online decision aid. All results will be reported to parents by trained genetic professionals (genetic counselors and clinical geneticists)

Inclusion criteria

• Uncomplicated pregnancy and healthy newborn

Exclusion criteria

• Abnormalities such as major malformation or chromosomal disorder detected prenatally or significant complications during pregnancy or at the time of delivery.