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.
Int J Neonatal Screen. 2023 Oct 30;9(4):63. doi: 10.3390/ijns9040063. ABSTRACT Rapid advances in the screening, diagnosis, and treatment of genetic disorders have increased the number of conditions that can be detected through universal newborn screening (NBS). However, the addition of conditions to the Recommended Uniform Screening Panel (RUSP) and the implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here, we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders worldwide. The NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs, including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases, have utilized NBSTRN’s tools and, in turn, contributed
National Academies of Sciences, Engineering, and Medicine. 2023. The Promise and Perils of Next-Generation DNA Sequencing at Birth: Proceedings of a Workshop–in Brief. Washington, DC: The National Academies Press. https://doi.org/10.17226/2724 Pilot programs are employing whole genome sequencing and whole exome sequencing during the newborn phase both within the United States and internationally. While sequencing offers the opportunity to screen for treatable but not clinically evident conditions early in a child’s life, it raises a host of ethical, legal, and social questions for experts, including parents, to consider. The National Academies Roundtable on Genomics and Precision Health hosted experts from health care, industry, academia, the federal and state governments, and patient and consumer advocacy groups for a June 2023 workshop. Participants, including RCIGM investigator Nathaly Sweeney, explored the potential benefits and harms, data security, and health equity considerations for the widespread utilization of newborn genome sequencing in the U.S. This publication summarizes
Clin Ther. 2023 Jul 8:S0149-2918(23)00220-5. doi: 10.1016/j.clinthera.2023.06.014. Online ahead of print. ABSTRACT PURPOSE: Diagnostic genomic research has the potential to directly benefit participants. This study sought to identify barriers to equitable enrollment of acutely ill newborns into a diagnostic genomic sequencing research study. METHODS: We reviewed the 16-month recruitment process of a diagnostic genomic research study enrolling newborns admitted to the neonatal intensive care unit at a regional pediatric hospital that primarily serves English- and Spanish-speaking families. Differences in eligibility, enrollment, and reasons for not enrolling were examined as functions of race/ethnicity and primary spoken language. FINDINGS: Of the 1248 newborns admitted to the neonatal intensive care unit, 46% (n = 580) were eligible, and 17% (n = 213) were enrolled. Of the 16 languages represented among the newborns’ families, 4 (25%) had translated consent documents. Speaking a language other than English or Spanish increased a newborn’s likelihood of being
Am J Hum Genet. 2023 Jun 1;110(6):1017. doi: 10.1016/j.ajhg.2023.05.004. NO ABSTRACT PMID:37267897 DOI:10.1016/j.ajhg.2023.05.004
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 types of DBS. We tested these methods in DBS from 25 individuals who had previously undergone diagnostic, clinical WGS and 29 randomly selected DBS cards collected for NBS from the California State Biobank. While gDNA from DBS had significantly less yield than from EDTA blood from the same individuals, it
Am J Med Genet C Semin Med Genet. 2022 Oct 11. doi: 10.1002/ajmg.c.32005. Online ahead of print. ABSTRACT In this Dispatch from Biotech, we briefly review the urgent need for extensive expansion of newborn screening (NBS) by genomic sequencing, and the reasons why early attempts had limited success. During the next decade transformative developments will continue in society and in the pharmaceutical, biotechnology, informatics, and medical sectors that enable prompt addition of genetic disorders to NBS by rapid whole genome sequencing (rWGS) upon introduction of new therapies that qualify them according to the Wilson and Jungner criteria (Wilson, J. M. G., & Jungner, G., World Health Organization. (1968). Principles and Practice of Screening for Disease. World Health Organization. Retrieved from https://apps.who.int/iris/handle/10665/37650). Herein we describe plans, progress, and clinical trial designs for BeginNGS (Newborn Genome Sequencing to end the diagnostic and therapeutic odyssey), a new international, pre-competitive, public-private consortium that proposes
