NEWBORN GENOMIC SEQUENCING

to end the diagnostic odyssey

Birth… the beginning of a family’s story.

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.

Imagine if we could change the narrative for those families from the very start.

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Rady Children’s Institute for Genomic Medicine is helping to rewrite the story for infants with rare diseases through BeginNGS^TM.

BeginNGS is a novel health care delivery system designed to screen newborns for genetic diseases — and connect their doctors with effective interventions.

Genetic diseases are chronic, progressive, and can be life-threatening.

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.

Sometimes the solution is as simple as a vitamin supplement.

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 helps ensure each baby is screened for genetic conditions for which interventions exist, and helps physicians provide effective interventions in a timely manner.

What is BeginNGS?

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.

As our understanding of genetic diseases grows, and the pace of therapeutic innovation accelerates, newborn screening by WGS may provide a more dynamic way of expanding the number of conditions.

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™

Slide

By rewriting the beginning, we can help families end their diagnostic and therapeutic odysseys so they can fill their stories with hope.

— Stephen Kingsmore, MD, DSc
President & CEO, Rady Children's Institute for Genomic Medicine

Slide

Early diagnosis of rare disease patients will open the door to ongoing monitoring of symptoms and gathering of critical natural history data

— Charlene Son Rigby
CEO, Rare-X

Why Now?

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.

Join Us

Interested in partnering with us or learning more about the project?

How It Will Work

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.

Ready to Learn More?

Media Coverage

September 12, 2023

FIERCE Healthcare

How Rapid Whole Genome Sequencing Can Change the Rare Disease Game for Every Newborn

FIERCE Healthcare: The rare disease journey can be long and difficult. rWGS could offer newborns a greater chance of successful diagnosis and intervention at birth.

Media Coverage

September 8, 2023

AJMCtv

Dr Stephen Kingsmore Describes the Participants of the BeginNGS Consortium

Dr. Stephen Kingsmore explains how the BeginNGS consortium members help the project to continually evolve.

Media Coverage

August 29, 2023

AJMCtv

Dr. Stephen Kingsmore Highlights Disparities Seen in Genetic Testing

AJMCtv: Stephen Kingsmore discusses the types of disparities seen in genetic testing as the BeginNGS phase 2 clinical trial is underway.

Media Coverage

August 14, 2023

Becker's Healthcare Podcast

Interview with Patricio A. Frias, President and CEO of Rady Children’s Hospital – San Diego

Becker's Healthcare Podcast: RCHSD President and CEO Patricio A. Frias shares the exciting innovative research being conducted at Rady Children's Institute for Genomic Medicine.

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Assessing Diversity in Newborn Genomic Sequencing Research Recruitment: Race/Ethnicity and Primary Spoken Language Variation in Eligibility, Enrollment, and Reasons for Declining

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

Response to Grosse et al

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

Scalable, high quality, whole genome sequencing from archived, newborn, dried blood spots

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

Dispatches from Biotech beginning BeginNGS: Rapid newborn genome sequencing to end the diagnostic and therapeutic odyssey

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

A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases

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

An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases

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

NEWBORN GENOMIC SEQUENCING

to end the diagnostic odyssey

Birth… the beginning of a family’s story.

Imagine if we could change the narrative for those families from the very start.

Rady Children’s Institute for Genomic Medicine is helping to rewrite the story for infants with rare diseases through BeginNGSTM.

Genetic diseases are chronic, progressive, and can be life-threatening.

Sometimes the solution is as simple as a vitamin supplement.

BeginNGS helps ensure each baby is screened for genetic conditions for which interventions exist, and helps physicians provide effective interventions in a timely manner.

What is BeginNGS?

As our understanding of genetic diseases grows, and the pace of therapeutic innovation accelerates, newborn screening by WGS may provide a more dynamic way of expanding the number of conditions.

Screening

Rapid Intervention

By rewriting the beginning, we can help families end their diagnostic and therapeutic odysseys so they can fill their stories with hope.

Early diagnosis of rare disease patients will open the door to ongoing monitoring of symptoms and gathering of critical natural history data

Why Now?

Join Us

How It Will Work

Ready to Learn More?

Upcoming BeginNGS Presentations & Events

2023 International Conference on Newborn Sequencing

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Rady Children’s Institute for Genomic Medicine is helping to rewrite the story for infants with rare diseases through BeginNGS^TM.