The BabySeq project: implementing genomic sequencing in newborns

Holm, Ingrid A.; Agrawal, Pankaj B.; Ceyhan‐Birsoy, Ozge; Christensen, Kurt D.; Fayer, Shawn; Frankel, Leslie A.; Genetti, Casie A.; Krier, Joel B.; LaMay, Rebecca C.; Levy, Harvey L.; McGuire, Amy L.; Parad, Richard B.; Park, Peter J.; Pereira, Stacey; Rehm, Heidi L.; Schwartz, Talia S.; Waisbren, Susan E.; Yu, Timothy W.; Green, Robert C.; Beggs, Alan H.

doi:10.1186/s12887-018-1200-1

Cited by 145 publications

(135 citation statements)

References 36 publications

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“…Today, with over 55,000 commercially available clinical genetic tests (https://www.ncbi.nlm.nih.gov/gtr/) and new tests entering the market daily, genome sequencing is increasingly used in routine clinical care for diagnostic purposes. Other emerging uses of genomic information to inform clinical decision making exist in areas like cancer detection and treatment (Deng and Nakamura, 2017), pre-and perinatal testing, (Hui and Bianchi, 2017;Peters et al, 2015), inpatient management of critically ill infants (Farnaes et al, 2018;Petrikin et al, 2015), and care of healthy and sick newborns (Holm et al, 2018) and adults (Vassy et al, 2014).…”

Section: The Rise Of Genomics In Medicinementioning

confidence: 99%

Personalized Medicine and the Power of Electronic Health Records

Abul‐Husn

Kenny

2019

Cell

258

162

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Personalized medicine has largely been enabled by the integration of genomic and other data with electronic health records (EHRs) in the United States and elsewhere. Increased EHR adoption across various clinical settings and the establishment of EHR-linked population-based biobanks provide unprecedented opportunities for the types of translational and implementation research that drive personalized medicine. We review advances in the digitization of health information and the proliferation of genomic research in health systems and provide insights into emerging paths for the widespread implementation of personalized medicine.

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Section: The Rise Of Genomics In Medicinementioning

confidence: 99%

Personalized Medicine and the Power of Electronic Health Records

Abul‐Husn

Kenny

2019

Cell

258

162

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“…Recently, the BabySeq Project (a part of NSIGHT), evaluated newborn diseases using genome scale sequencing in a randomized clinical trial pilot. The cohort studied included both well newborns and those admitted to a neonatal intensive care unit [20,21]. In a cohort of 159 newborns that underwent genome scale NGS based whole exome sequencing (WES), one carrier of a pathogenic GAA variant was identified.…”

Section: Genome Scale Data and Its Impact On Pd Screeningmentioning

confidence: 99%

Second Tier Molecular Genetic Testing in Newborn Screening for Pompe Disease: Landscape and Challenges

Smith

Bainbridge

Parad

et al. 2020

IJNS

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Pompe disease (PD) is screened by a two tier newborn screening (NBS) algorithm, the first tier of which is an enzymatic assay performed on newborn dried blood spots (DBS). As first tier enzymatic screening tests have false positive results, an immediate second tier test on the same sample is critical in resolving newborn health status. Two methodologies have been proposed for second tier testing: (a) measurement of enzymatic activities such as of Creatine/Creatinine over alpha-glucosidase ratio, and (b) DNA sequencing (a molecular genetics approach), such as targeted next generation sequencing. (tNGS). In this review, we discuss the tNGS approach, as well as the challenges in providing second tier screening and follow-up care. While tNGS can predict genotype-phenotype effects when known, these advantages may be diminished when the variants are novel, of unknown significance or not discoverable by current test methodologies. Due to the fact that criticisms of screening algorithms that utilize tNGS are based on perceived complexities, including variant detection and interpretation, we clarify the actual limitations and present the rationale that supports optimizing a molecular genetic testing approach with tNGS. Second tier tNGS can benefit clinical decision-making through the use of the initial NBS DBS punch and rapid turn-around time methodology for tNGS, that includes copy number variant analysis, variant effect prediction, and variant ‘cut-off’ tools for the reduction of false positive results. The availability of DNA sequence data will contribute to the improved understanding of genotype-phenotype associations and application of treatment. The ultimate goal of second tier testing should enable the earliest possible diagnosis for the earliest initiation of the most effective clinical interventions in infants with PD.

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“…Some studies may also offer to return medically actionable secondary results as recommended by the ACMG while others may offer to return genomic screening results specific to study aims. 9,[11][12][13] Offering large amounts of genomic information to participants can make decisionmaking about which results to learn increasingly complex. When faced with such a complex decision, individuals may experience decisional conflict, which is a "personal uncertainty about which course of action to take when choice among competing options involves risk, regret or challenge to personal life values."…”

Section: Introductionmentioning

confidence: 99%

Decisional conflict among adolescents and parents making decisions about genomic sequencing results

et al. 2019

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Genomic testing of adolescents is increasing yet engaging them in decision-making is not routine. We assessed decisional conflict in adolescents and a parent making independent decisions about actual genomic testing results and factors that influenced their choices. We enrolled 163 dyads consisting of an adolescent (13-17 years) not selected based on a specific clinical indication and one parent. After independently choosing categories of conditions to learn for the adolescent, participants completed the validated Decisional Conflict Scale and a survey assessing factors influencing their respective choices. Adolescents had higher decisional conflict scores than parents (15.6 [IQR:4.7-25.6] vs 9.4 [IQR:1.6-21.9]; P = .0007). Adolescents with clinically significant decisional conflict were less likely to choose to learn all results than adolescents with lower decisional conflict (19.6% vs 80.4%; P < .0001) and less likely to report their choices were influenced by actionability of results (33.3% vs 18.9%; P = .044) and feeling confident they can deal with the results (71.2% vs 91.9%; P = .0005). Our findings suggest higher decisional conflict in adolescents may influence the type and amount of genomic results they wish to learn. Additional research assessing decisional conflict and factors influencing testing choices among adolescents in clinical settings are required. recommended by the ACMG while others may offer to return genomic screening results specific to study aims. 9,[11][12][13] Offering large amounts of genomic information to participants can make decisionmaking about which results to learn increasingly complex. When faced with such a complex decision, individuals may experience decisional conflict, which is a "personal uncertainty about which course of action to take when choice among competing options involves risk, regret or challenge to personal life values." 14 Making decisions about learning genomic information can be particularly challenging for asymptomatic minors -especially if they are offered the option to learn about carrier status or adult onset conditions that are not actionable in childhood. Concerns about learning carrier results or adult-onset conditions include psychosocial harms such as undue loss of autonomy and privacy; stress, anxiety and stigmatization. 15,16 However, benefits also include being aware of treatment and screening options, not being blindsided by a diagnosis at a later age, and the ability to make informed reproductive decisions and prompt life changes. 17 Literature focusing on the return of secondary genomic results has mainly focused on understanding the preferences of adults and parents with children who are at risk of or previously diagnosed with a genetic condition. 16,18,19 Adolescents' preferences about secondary findings and factors that influence their decisions to learn genomic information have largely been unexplored. In addition, most studies have involved hypothetical return of secondary findings and may not accurately depict preferences of the participa...

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The BabySeq project: implementing genomic sequencing in newborns

Cited by 145 publications

References 36 publications

Personalized Medicine and the Power of Electronic Health Records

Personalized Medicine and the Power of Electronic Health Records

Second Tier Molecular Genetic Testing in Newborn Screening for Pompe Disease: Landscape and Challenges

Decisional conflict among adolescents and parents making decisions about genomic sequencing results

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