Patient decisions for disclosure of secondary findings among the first 200 individuals undergoing clinical diagnostic exome sequencing

Abstract

Purpose:Exome sequencing of a single individual for a clinical indication may result in the identification of incidental deleterious variants unrelated to the indication for testing (secondary findings). Given the recent availability of clinical exome testing, there is a limited knowledge regarding the disclosure preferences and impact of secondary findings in a clinical diagnostic setting. In this article, we provide preliminary data regarding the preferences for secondary findings results disclosure based on the first 200 families referred to Ambry Genetics for diagnostic exome sequencing.Methods:Secondary findings were categorized into four groups in the diagnostic exome sequencing consent: carrier status of recessive disorders, predisposition to later-onset disease, predisposition to increased cancer risk, and early-onset disease. In this study, we performed a retrospective analysis of patient responses regarding the preferences for secondary findings disclosure.Results:The majority of patients (187/200; 93.5%) chose to receive secondary results for one or more available categories. Adult probands were more likely than children to opt for blinding of secondary data (16 vs. 4%, respectively). Among responses for blinding, preferences were evenly scattered among categories.Conclusion:These data represent the unprecedented results of a large reference laboratory providing clinical exome sequencing. We report, for the first time, the preferences of patients and families for the receipt of secondary findings based on clinical genome sequencing. Overwhelmingly, families undergoing exome sequencing opt for the disclosure of secondary findings. The data may have implications regarding the development of guidelines for secondary findings reporting among patients with severe and/or life-threatening disease undergoing clinical genomic sequencing.

Unsolicited findings of next-generation sequencing for tumor analysis within a Dutch consortium: clinical daily practice reconsidered

“…[23][24][25] Stimulating the development of educational materials that clearly communicate disease associations or the development of decision tools for patients and physician's is an open research field. 14,26 Further research is needed to compare different ways of disclosing results, also from patients' perspective and preferences in this field of rapid evolving NGS strategies in daily practice.…”

Application of Next-generation Sequencing in Clinical Molecular Diagnostics

“…The selection of these 56 genes is relied on pathogenicity and the possibility of the genetic result leading to a specific therapeutic option ("actionable" findings). However, there is an in time discussion how to best proceed with incidental findings 72,73 . Whereas in the research setting, these incidental findings usually do not absorb much attention, it is notable that there is growing intrigue in receiving information about incidental findings on the patient side 73 .…”

“…However, there is an in time discussion how to best proceed with incidental findings 72,73 . Whereas in the research setting, these incidental findings usually do not absorb much attention, it is notable that there is growing intrigue in receiving information about incidental findings on the patient side 73 . This is also reflected by the increasing providing and popularity of direct-to-consumer genetic testing (DTCGT).…”

Genome-Wide Sequencing for Prenatal Detection of Fetal Single-Gene Disorders

“…Whether testing for adult-onset disorders in children, and by deduction prenatally, should be limited is a matter of debate on its own (Mand et al 2012;Anderson et al 2014), but existing guidelines were directed toward actively seeking testing for adult-onset conditions and predated the era of genome-wide sequencing with its potential to uncover such findings incidentally and unintentionally. Recent survey studies have indicated that probands and parents of children undergoing WES are interested in having incidental findings disclosed (Townsend et al 2012;Fernandez et al 2014;Shahmirzadi et al 2014).…”