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.
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
Am J Hum Genet. 2022 Aug 18:S0002-9297(22)00355-X. doi: 10.1016/j.ajhg.2022.08.003. Online ahead of print. ABSTRACT Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders by treatment before symptom onset. In many genetic diseases, however, outcomes remain poor because NBS has lagged behind drug development. Rapid whole-genome sequencing (rWGS) is attractive for comprehensive NBS because it concomitantly examines almost all genetic diseases and is gaining acceptance for genetic disease diagnosis in ill newborns. We describe prototypic methods for scalable, parentally consented, feedback-informed NBS and diagnosis of genetic diseases by rWGS and virtual, acute management guidance (NBS-rWGS). Using established criteria and the Delphi method, we reviewed 457 genetic diseases for NBS-rWGS, retaining 388 (85%) with effective treatments. Simulated NBS-rWGS in 454,707 UK Biobank subjects with 29,865 pathogenic or likely pathogenic variants associated with 388 disorders had a true negative rate (specificity) of 99.7% following root cause analysis. In 2,208 critically ill children
Nat Commun. 2022 Jul 26;13(1):4057. doi: 10.1038/s41467-022-31446-6. While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports (https://gtrx.radygenomiclab.com). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in
