Abstract & Overview
Newborn screening (NBS) is a well-known and widely accepted activity in public health. The majority of babies born in the United States are screened via a biochemical blood test for conditions that are difficult to diagnose but require treatment soon after birth. NBS began in the 1960s as a blood test for phenylketonuria (PKU) and additional disorders were added to the screening panel as technological advancements, such as tandem mass spectrometry (MS/MS), improved detection of many metabolic disorders. Based on the guidelines set forth by the American College of Medical Genetics, the U.S. Department of Health Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children selects disorders for the recommended uniform screening panel (RUSP) if (1) they can be detected 24-48 hours after birth and would not otherwise be detected, (2) there is reliable screening method with appropriate sensitivity and specificity and (3) there are benefits of early detection and treatment. NBS has been successful; however, the technology used in medicine is quickly advancing and NBS programs are faced with the challenge of incorporating new technology into their screening protocol to improve detection of disorders. Next generation sequencing (NGS), including whole exome sequencing (WES), is one of these new technologies. WES identifies the DNA sequence of the coding region of the genome, where it is believed 85% of disease causing genetic variation occurs. With its relatively low cost and ability to provide detailed genetic information, WES is quickly becoming a tool with the potential to revolutionize public health, however, the impact of its use in the clinic for the benefit on overall health remains unknown.