North Carolina Newborn Exome Sequencing for Universal Screening (NC_NEXUS)

University of North Carolina (UNC)

Status: Completed

Conditions: Metabolism, Inborn Errors; Hearing Loss; Hereditary Disease

Treatments: Genetic: Well infant, whole exome sequencing; Genetic: Diagnosed, whole exome sequencing

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02826694

5U19HD077632 (U.S. NIH Grant/Contract)

13-2409

Details and patient eligibility

About

The NC NEXUS research study is exploring the utility of next generation sequencing in newborn screening and parental decision making. The National Institutes of Health (NICHD and NHGRI) are co-funding this study under a single U-19.

Full description

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)

Enrollment: 106 patients

Sex: All

Ages: 1 hour to 5 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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106 participants in 2 patient groups

Well infant, whole exome sequencing

Other group

Description:

Healthy infants and their parents enrolled in the study prenatally will participate. After the infant is born saliva sample will be collected for DNA extraction and whole exome sequencing will be done.

Treatment:

Genetic: Well infant, whole exome sequencing

Diagnosed, whole exome sequencing

Other group

Description:

Infants and children with diagnosed conditions whose parents enroll in the study and consent to having their child sequenced will have saliva samples obtained and whole exome sequencing will be done on extracted DNA.

Treatment:

Genetic: Diagnosed, whole exome sequencing