"Possibly positive or certainly uncertain?": participants' responses to uncertain diagnostic results from exome sequencing.

PurposeClinical genome sequencing produces uncertain diagnostic results, raising concerns about how to communicate the method's inherent complexities in ways that reduce potential misunderstandings and harm. This study investigates clinicians' communications and patient/participant responses to uncertain diagnostic results arising from a clinical exome sequencing research study, contributing empirical data to the debate surrounding disclosure of uncertain genomic information.MethodsWe investigated the communication and impact of uncertain diagnostic results using ethnographic observations of result disclosures with 21 adults and 11 parents of child patients, followed by two semistructured interviews with these same participants.ResultsParticipants understood their uncertain results in ways that were congruent with clinical geneticists' communications. They followed recommendations for further consultation, although family testing to resolve uncertainty was not always done. Participants were prepared for learning an uncertain result and grasped the key concept that it should not be used to guide health-care or other decisions. They did not express regret for having learned the uncertain result; most regarded it as potentially valuable in the future.ConclusionThis study suggests that uncertain diagnostic results from genome sequencing can be relayed to patients in ways they can understand and consistent with providers' interpretations, without causing undue harm.

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

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.