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. 2022 Jun;190(2):243-256.
doi: 10.1002/ajmg.c.32005. Epub 2022 Oct 11.

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

Stephen F Kingsmore  1 ; BeginNGS Consortium
Affiliations

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

Stephen F Kingsmore et al. Am J Med Genet C Semin Med Genet. 2022 Jun.

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 to implement a self-learning healthcare delivery system for screening all newborns for over 400 hundred genetic diseases, diagnostic confirmation, implementation of effective treatment, and acceleration of orphan drug development. We invite investigators and stakeholders worldwide to join the consortium in a prospective, multi-center, international trial of the clinical utility and cost effectiveness of BeginNGS.

Keywords: genetic disease; management guidance; molecular diagnosis; newborn screening; orphan drug; rapid whole genome sequencing.

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Conflict of interest statement

None.

Figures

FIGURE 1
FIGURE 1
Graphical abstract of the scope and aims of BeginNGS™. From https://radygenomics.org/2022/rcigm‐launches‐program‐to‐advance‐newborn‐screening‐for‐treatable‐genetic‐diseases
FIGURE 2
FIGURE 2
Stages of development of BeginNGS™ and key milestones. Green circle, completed. Yellow circle, in progress. Teal circles, not started. R1, retrospective study 1. R2, retrospective study 2. P1, prospective study 1. P2, prospective study 2. CLIA, clinical laboratory improvements act
FIGURE 3
FIGURE 3
Methods used to qualify disorders for inclusion in BeginNGS™. GTRx, Genome‐to‐Treatment virtual acute management guidance system (Figure 4). Group A, disorders for which the Delphi panel consensus was that the Phase ii criteria were met. Group B, disorders for which the natural history was not yet well understood or for which early treatment was not yet known to improve outcome but that were retained for prospective clinical study. ICU, intensive care unit; NBS, newborn screening; rWGS, rapid whole genome sequencing
FIGURE 4
FIGURE 4
Example of GTRx acute management guidance for Timothy syndrome (MIM: 601005)
FIGURE 5
FIGURE 5
Schematic showing the roles of various stakeholders in BeginNGS™
See this image and copyright information in PMC

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