But for families of babies born with a rare genetic disease, the story is one fraught with challenges on their journey to an accurate diagnosis and appropriate care.
BeginNGS is a novel health care delivery system designed to screen newborns for genetic diseases — and connect their doctors with effective interventions.
They may not appear until later in childhood; however, the effects may begin before symptoms manifest. The effects may be irreversible if not diagnosed and treated.
Other times, the baby can receive cutting-edge gene therapy and grow up to be a typical healthy child, like Fitz Kettler, pictured here.
BeginNGS is an RCIGM-led pilot that uses whole genome sequencing (WGS) as a screening tool for newborns, to identify genetic conditions before infants get sick. The BeginNGS pilot is not about replacing the current biochemical newborn screening approach (for roughly 60 known conditions) – rather, it is a complement to the newborn screening processes and infrastructure that are already in place.
Technological advances in whole genome sequencing have made it possible to return test results in just a few days at a lower cost.
Since the whole genome is sequenced, the screening can be rapidly expanded to include new disorders as effective interventions become available.
Screening newborns for ~400 genetic diseases with known intervention options using rWGS
Identifying rare disease earlier to facilitate access to Rapid Precision Medicine™
— Stephen Kingsmore, MD, DSc
President & CEO, Rady Children's Institute for Genomic Medicine
— Charlene Son Rigby
CEO, Rare-X
There are over 30 million rare disease patients in the United States and over 5,000 rare disease clinical trials underway. Ending the diagnostic and therapeutic odyssey is finally within our grasp. Without disruptive progress, precision medicine at scale isn’t possible. BeginNGS will help us identify rare disease patients earlier, increase clinical trial enrollment and rapidly progress rare disease treatment.
Interested in partnering with us or learning more about the project?
This pilot includes birthing hospitals throughout the U.S. and abroad.
Blood-spot samples will be collected at the time of birth and sent to the lab where WGS will be performed.
Genomic analysis and interpretation will be performed for ~400 early onset actionable genetic conditions.
If a positive screening result is detected, the treating physician will be provided with access to resources on medical management and available interventions. They will then discuss next steps with the family. Licensed and board-certified genetic counselors will be available for consultation.
Methods Mol Biol. 2023;2621:217-239. doi: 10.1007/978-1-0716-2950-5_12. ABSTRACT Upon admission to intensive care units (ICU), the differential diagnosis of almost all infants with diseases of unclear etiology includes single locus genetic diseases. Rapid whole genome sequencing (rWGS), including sample preparation, short-read sequencing-by-synthesis, informatics pipelining, and semiautomated interpretation, can now identify nucleotide and structural variants associated with most genetic diseases with robust analytic and diagnostic performance in as little as 13.5 h. Early diagnosis of genetic diseases transforms medical and surgical management of infants in ICUs, minimizing both the duration of empiric treatment and the delay to start of specific treatment. Both
Genome Med. 2023 Mar 16;15(1):18. doi: 10.1186/s13073-023-01166-7. ABSTRACT BACKGROUND: Rapidly and efficiently identifying critically ill infants for whole genome sequencing (WGS) is a costly and challenging task currently performed by scarce, highly trained experts and is a major bottleneck for application of WGS in the NICU. There is a dire need for automated means to prioritize patients for WGS. METHODS: Institutional databases of electronic health records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for rapid and whole genome sequencing (rWGS and WGS) directly from clinical notes. Our
NPJ Genom Med. 2023 Feb 14;8(1):5. doi: 10.1038/s41525-023-00349-w. ABSTRACT Universal newborn screening (NBS) is a highly successful public health intervention. Archived dried bloodspots (DBS) collected for NBS represent a rich resource for population genomic studies. To fully harness this resource in such studies, DBS must yield high-quality genomic DNA (gDNA) for whole genome sequencing (WGS). In this pilot study, we hypothesized that gDNA of sufficient quality and quantity for WGS could be extracted from archived DBS up to 20 years old without PCR (Polymerase Chain Reaction) amplification. We describe simple methods for gDNA extraction and WGS library preparation from several
