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. 2016 Nov;38(8):1303-1317.
doi: 10.1111/1467-9566.12460. Epub 2016 Aug 19.

The nuanced negative: Meanings of a negative diagnostic result in clinical exome sequencing

Debra Skinner  1 , Kelly A Raspberry  2 , Martha King  3
Affiliations

The nuanced negative: Meanings of a negative diagnostic result in clinical exome sequencing

Debra Skinner et al. Sociol Health Illn. 2016 Nov.

Abstract

Genomic sequencing technology is moving rapidly from the research setting into clinical medicine but significant technological and interpretive challenges remain. Exome sequencing (ES) in its recent clinical application provides a genetic diagnosis in about 25 per cent of cases (Berg 2014). While this diagnostic yield is substantial, it also indicates that in a majority of cases, patients are receiving negative results (i.e. no explanatory genetic variant found) from this technology. There are a number of uncertainties regarding the meaning of a negative result in the current context of ES. A negative result may be due to current technological limitations that hinder detection of disease-causing variants or to gaps in the knowledge base that prohibit accurate interpretation of their pathogenicity; or it may indicate that there is not a genetic etiology for the disorder. In this paper we examine the uncertainties and nuances of the negative result from genome sequencing and how both clinicians and patients make meaning of it as revealed in ethnographic observations of the clinic session where results are returned, and in interviews with patients. We find that clinicians and patients construct the meaning of a negative result in ways that are uncertain, contingent, and multivalent; but invested with optimism, promise, and potentiality.

Keywords: clinical practice; diagnostic results; genome sequencing; meaning making; return of results; uncertainty.

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References

    1. Armstrong N, Eborall H. The sociology of medical screening: past, present and future. Sociology of Health and Illness. 2012;34(2):161–176. - PubMed
    1. Atkinson P, Featherstone K, Gregory M. Kinscapes, timescapes and genescapes: families living with genetic risk. Sociology of Health and Illness. 2013;35(8):1227–1241. - PubMed
    1. Berg JS. Genome-scale sequencing in clinical care: establishing molecular diagnoses and measuring value. Journal of the American Medical Association. 2014;312(18):1865–1867. - PubMed
    1. Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. The New England Journal of Medicine. 2014;370(25):2418–2425. - PubMed
    1. Brown N. Hope against hype: accountability in biopasts, presents and futures. Science Studies. 2003;16(2):3–21.

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