ArticleEuropean journal of human genetics : EJHG2015
Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects.
Article in European journal of human genetics : EJHG, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Unsolved challenges of clinical whole-exome sequencing: a systematic literature review of end-users' views.BMC medical genomics · 2016Pooled it
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- Cross-Site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms for the CIMAC-CIDC Network.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
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- Clinical genetics in transition-a comparison of genetic services in Estonia, Finland, and the Netherlands.Journal of community genetics · 2021Article
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- Consent for clinical genome sequencing: considerations from the Clinical Sequencing Exploratory Research Consortium.Personalized medicine · 2019Article
- Lack of evidence for a causal role of CALR3 in monogenic cardiomyopathy.European journal of human genetics : EJHG · 2018Article
- Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities.EJIFCC · 2018Article
- A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.Scientific reports · 2017Article
- Whole-exome sequencing in pediatrics: parents' considerations toward return of unsolicited findings for their child.European journal of human genetics : EJHG · 2016Article
- Legal approaches regarding health-care decisions involving minors: implications for next-generation sequencing.European journal of human genetics : EJHG · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
48 authors at 12 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Implementation of next-generation DNA sequencing (NGS) technology into routine diagnostic genome care requires strategic choices. Instead of theoretical discussions on the consequences of such choices, we compared NGS-based diagnostic practices in eight clinical genetic centers in the Netherlands, based on genetic testing of nine pre-selected patients with cardiomyopathy. We highlight critical implementation choices, including the specific contributions of laboratory and medical specialists, bioinformaticians and researchers to diagnostic genome care, and how these affect interpretation and reporting of variants. Reported pathogenic mutations were consistent for all but one patient. Of the two centers that were inconsistent in their diagnosis, one reported to have found 'no causal variant', thereby underdiagnosing this patient. The other provided an alternative diagnosis, identifying another variant as causal than the other centers. Ethical and legal analysis showed that informed consent procedures in all centers were generally adequate for diagnostic NGS applications that target a limited set of genes, but not for exome- and genome-based diagnosis. We propose changes to further improve and align these procedures, taking into account the blurring boundary between diagnostics and research, and specific counseling options for exome- and genome-based diagnostics. We conclude that alternative diagnoses may infer a certain level of 'greediness' to come to a positive diagnosis in interpreting sequencing results. Moreover, there is an increasing interdependence of clinic, diagnostics and research departments for comprehensive diagnostic genome care. Therefore, we invite clinical geneticists, physicians, researchers, bioinformatics experts and patients to reconsider their role and position in future diagnostic genome care.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.