Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience

Porter, Kevin; Kauffman, Tia L.; Koenig, Barbara A.; Lewis, Katie; Rehm, Heidi L.; Richards, C. Sue; Strande, Natasha T.; Tabor, Holly K.; Wolf, Susan M.; Yang, Yaping; Amendola, Laura M.; Azzariti, Danielle R.; Berg, Jonathan S.; Bergstrom, Katie; Biesecker, Leslie G.; Biswas, Sawona; Bowling, Kevin M.; Chung, Wendy K.; Clayton, Ellen Wright; Conlin, Laura K.; Cooper, Gregory M.; Dulik, Matthew C.; Garraway, Levi A.; Green, Robert C; Hiatt, Susan M.; Jamal, Seema M.; Jarvik, Gail P.; Goddard, Katrina A.B.; Wilfond, Benjamin S.

doi:10.1002/mgg3.453

Cited by 14 publications

(8 citation statements)

References 44 publications

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“…Although feedback was largely positive, a minority of parents felt quality‐of‐life research is not highly valuable. Only two‐thirds of parents wished to be told the results at the time of consent, which is lower than for other types of research and may be influenced by different incentives . Negative reactions appeared to be driven by results seeming “obvious” or “nothing new,” consistent with preliminary findings suggesting parents “normalize” symptom distress .…”

Section: Discussionsupporting

confidence: 58%

Experience of parents receiving results from a quality‐of‐life study in pediatric advanced cancer: A report from the PediQUEST study

Bilodeau

Dussel

Wolfe

2019

Pediatric Blood & Cancer

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Little is known about the experience of parents receiving results of quality‐of‐life research in pediatric advanced cancer. The PediQUEST study participants who indicated interest in results during enrollment were mailed summarized findings and the Disseminating Quality‐of‐Life Research Questionnaire. Respondents (86%,12/14) reported feeling more than “a little” recognized, grateful, or satisfied to receive results. Concurrently, 43% (6/14) endorsed feeling more than “a little” sad, confused, or anxious. Nonetheless, 81% (13/16) prefer to be informed in the future. Although parents experience a spectrum of strong emotions, our findings suggest quality‐of‐life study results should be shared.

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Section: Discussionsupporting

confidence: 58%

Experience of parents receiving results from a quality‐of‐life study in pediatric advanced cancer: A report from the PediQUEST study

Bilodeau

Dussel

Wolfe

2019

Pediatric Blood & Cancer

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“…Many of these landmark projects have recently reported results, establishing evaluation frameworks and providing evidence on the diagnostic, clinical, and economic value of genomic sequencing in specific patient groups, such as healthy and acutely unwell newborns; [18][19][20][21][22] individuals with complex, undiagnosed rare genetic conditions; 23,24 and those in specific healthcare settings, such as primarycare and cardiology clinics. [25][26][27] NHGRI projects are also addressing specific evidence gaps in the clinical delivery of genomic testing, such as the the return of secondary findings, [28][29][30] inter-laboratory consistency in variant interpretation, 31,32 integration of genomic resources with electronic records, 33 and sharing implementation and evaluation experience more broadly. [34][35][36][37] Tools for electronic phenotyping (Phenotype KnowledgeBase), clinical decision support (Clinical Decision Support KnowledgeBase), and implementation in resource-limited settings (IGNITE SPARK Toolbox) are openly available, and ClinGen plays a central role internationally in curating and disseminating consensus information on clinically relevant genes and variants.…”

Section: United Statesmentioning

confidence: 99%

Integrating Genomics into Healthcare: A Global Responsibility

Stark

Dolman

Manolio

et al. 2019

The American Journal of Human Genetics

292

235

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Genomic sequencing is rapidly transitioning into clinical practice, and implementation into healthcare systems has been supported by substantial government investment, totaling over US$4 billion, in at least 14 countries. These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to implementation and gathering evidence for wider adoption. We review the diversity of approaches and current progress made by national genomic-medicine initiatives in the UK, France, Australia, and US and provide a roadmap for sharing strategies, standards, and data internationally to accelerate implementation.

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“…From a molecular analysis standpoint, carrier findings reported in this study were similar to other studies. 10,[106][107][108][109] Interestingly, many of the variants we observed are milder or hypomorphic variants; in order to cause disease, these alleles must be in trans with a more severe variant in the same gene (e.g., the RBM8A c.À21G>A [p.?] variant and the HFE c.187C>G [p.His63Asp] variant).…”

Section: Additional Genomic Findingsmentioning

confidence: 94%

Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project

Roman

Crowley

Roche

et al. 2020

The American Journal of Human Genetics

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Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the participant's underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders and in 5 out of 28 ($18%) children with hearing loss. We discovered actionable findings in four participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal-recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in two children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.

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Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience

Abstract: Future translational genomics research projects will need to make decisions regarding whether and how to disclose carrier results. The CSER consortium experience identifies approaches that balance potential participant interest while limiting impact on project resources.

Cited by 14 publications

References 44 publications

Experience of parents receiving results from a quality‐of‐life study in pediatric advanced cancer: A report from the PediQUEST study

Experience of parents receiving results from a quality‐of‐life study in pediatric advanced cancer: A report from the PediQUEST study

Integrating Genomics into Healthcare: A Global Responsibility

Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project

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