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. 2023 May 1;6(5):e2312231.
doi: 10.1001/jamanetworkopen.2023.12231.

Perspectives of Rare Disease Experts on Newborn Genome Sequencing

Nina B Gold  1   2 , Sophia M Adelson  3   4 , Nidhi Shah  5   6   7 , Shardae Williams  3   4 , Sarah L Bick  2   7 , Emilie S Zoltick  3   8   9 , Jessica I Gold  10 , Alanna Strong  10   11 , Rebecca Ganetzky  10   11 , Amy E Roberts  2   12 , Melissa Walker  13   14 , Alexander M Holtz  7 , Vijay G Sankaran  2   15   16 , Ottavia Delmonte  17 , Weizhen Tan  2   18 , Ingrid A Holm  2   7   19 , Jay R Thiagarajah  2   20 , Junne Kamihara  2   15   16 , Jason Comander  21   22 , Emily Place  21   22 , Janey Wiggs  21   22 , Robert C Green  3   4   23   24
Affiliations

Perspectives of Rare Disease Experts on Newborn Genome Sequencing

Nina B Gold et al. JAMA Netw Open. .

Abstract

Importance: Newborn genome sequencing (NBSeq) can detect infants at risk for treatable disorders currently undetected by conventional newborn screening. Despite broad stakeholder support for NBSeq, the perspectives of rare disease experts regarding which diseases should be screened have not been ascertained.

Objective: To query rare disease experts about their perspectives on NBSeq and which gene-disease pairs they consider appropriate to evaluate in apparently healthy newborns.

Design, setting, and participants: This survey study, designed between November 2, 2021, and February 11, 2022, assessed experts' perspectives on 6 statements related to NBSeq. Experts were also asked to indicate whether they would recommend including each of 649 gene-disease pairs associated with potentially treatable conditions in NBSeq. The survey was administered between February 11 and September 23, 2022, to 386 experts, including all 144 directors of accredited medical and laboratory genetics training programs in the US.

Exposures: Expert perspectives on newborn screening using genome sequencing.

Main outcomes and measures: The proportion of experts indicating agreement or disagreement with each survey statement and those who selected inclusion of each gene-disease pair were tabulated. Exploratory analyses of responses by gender and age were conducted using t and χ2 tests.

Results: Of 386 experts invited, 238 (61.7%) responded (mean [SD] age, 52.6 [12.8] years [range 27-93 years]; 126 [52.9%] women and 112 [47.1%] men). Among the experts who responded, 161 (87.9%) agreed that NBSeq for monogenic treatable disorders should be made available to all newborns; 107 (58.5%) agreed that NBSeq should include genes associated with treatable disorders, even if those conditions were low penetrance; 68 (37.2%) agreed that actionable adult-onset conditions should be sequenced in newborns to facilitate cascade testing in parents, and 51 (27.9%) agreed that NBSeq should include screening for conditions with no established therapies or management guidelines. The following 25 genes were recommended by 85% or more of the experts: OTC, G6PC, SLC37A4, CYP11B1, ARSB, F8, F9, SLC2A1, CYP17A1, RB1, IDS, GUSB, DMD, GLUD1, CYP11A1, GALNS, CPS1, PLPBP, ALDH7A1, SLC26A3, SLC25A15, SMPD1, GATM, SLC7A7, and NAGS. Including these, 42 gene-disease pairs were endorsed by at least 80% of experts, and 432 genes were endorsed by at least 50% of experts.

Conclusions and relevance: In this survey study, rare disease experts broadly supported NBSeq for treatable conditions and demonstrated substantial concordance regarding the inclusion of a specific subset of genes in NBSeq.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr N. B. Gold reported receiving personal fees from Newspring Capital, Pfizer, and RCG Consulting; grants from the National Institutes of Health (NIH) and Greenwall Foundation; and an Eleanor and Miles Shore faculty development award outside the submitted work. Dr Shah reported serving as a scientific advisor for the Neuberg Center for Genomic Medicine. Dr Ganetzky reported receiving personal fees from Nurture Genomics during the conduct of the study and personal fees from Minovia Therapeutics outside the submitted work. Dr Walker reported receiving grant U01 HG007690 from the National Human Genome Research Institute; serving as a consortium co-investigator for the NIH Undiagnosed Disease Network, which has been supported by this U01 within the past 36 months outside the submitted work; having a patent pending (US Provisional Patent Application 63/034,740, Methods of Detecting Mitochondrial Diseases; The General Hospital Corporation, Children’s Medical Center Corporation, President and Fellows of Harvard College, The Broad Institute, and Massachusetts Institute of Technology [applicants] filed June 4, 2020); and receiving an honorarium in the past 3 years for writing board review questions for the American Academy of Neurolgoy. Dr Sankaran reported consulting fees from Novartis, Branch Biosciences, and Ensoma outside the submitted work. Dr Tan reported membership on an advisory board for Horizon Pharmaceuticals outside the submitted work. Dr Kamihara reported her spouse receiving consulting fees from ROME Therapeutics, Tekla Capital, Moderna, Ikena Oncology, Foundation Medicine, NanoString Technologies, and Pfizer; being a founder and having equity in ROME Therapeutics, PanTher Therapeutics, and TellBio; and receiving research support from ACD-Biotechne, PureTech Health, Ribon Therapeutics, and Incyte outside the submitted work. Dr Comander reported receiving research funding and consulting fees from companies studying inherited retinal disease genes for work not relevant to the topic of this article. Dr Wiggs reported receiving consulting fees from Editas outside the submitted work. Dr Green reported receiving consulting fees from AIA, Allelica, Atria, Fabric, Genome Web, Genomic Life, Verily, and VinBigData and being co-founder of Genome Medical and Nurture Genomics outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Experts’ Perspectives on the Scope of Disorders Included in Newborn Genome Sequencing
Experts were asked to indicate whether they agreed with 6 statements regarding the types of disorders that should be included in newborn genome sequencing.
Figure 2.
Figure 2.. Distribution of Expert Concordance for the Inclusion of Gene-Disease Pairs in Newborn Genome Sequencing
Among 649 gene-disease pairs in the survey, each was endorsed by at least 11.8% of experts. Overall, 25 gene-disease pairs were endorsed by 85% or more of the experts.
See this image and copyright information in PMC

References

    1. El-Hattab AW, Almannai M, Sutton VR. Newborn screening: history, current status, and future directions. Pediatr Clin North Am. 2018;65(2):389-405. doi:10.1016/j.pcl.2017.11.013 - DOI - PubMed
    1. Fabie NAV, Pappas KB, Feldman GL. The current state of newborn screening in the United States. Pediatr Clin North Am. 2019;66(2):369-386. doi:10.1016/j.pcl.2018.12.007 - DOI - PubMed
    1. Baird PA. Genetics and health care: a paradigm shift. Perspect Biol Med. 1990;33(2):203-213. doi:10.1353/pbm.1990.0009 - DOI - PubMed
    1. Kerruish NJ, Robertson SP. Newborn screening: new developments, new dilemmas. J Med Ethics. 2005;31(7):393-398. doi:10.1136/jme.2004.008219 - DOI - PMC - PubMed
    1. Green RC, Rehm HL, Kohane IS. Clinical genome sequencing. In: Ginsburg GS, Willard HF, eds. Genomic and Personalized Medicine. 2nd ed. Academic Press; 2013:102-122. doi:10.1016/B978-0-12-382227-7.00009-4 - DOI

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