Disclosure of clinically actionable genetic variants to thoracic aortic dissection biobank participants

• Published in: BMC medical genomics 2021-03, Vol.14 (1), p.66-12, Article 66
• Main Authors: Beil, Adelyn, Hornsby, Whitney, Uhlmann, Wendy R, Aatre, Rajani, Arscott, Patricia, Wolford, Brooke, Eagle, Kim A, Yang, Bo, McNamara, Jennifer, Willer, Cristen, Roberts, J Scott
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aorta; Aorta, Thoracic; Aortic Aneurysm, Thoracic - genetics; Aortic dissection; Aortic Dissection - genetics; Biobank; Biobanks; Biological Specimen Banks; Cardiovascular disease; Care and treatment; Communication; Diagnosis; Disclosure; Dissecting aneurysm; Dissection; Dissection, Thoracic Aorta; Evaluation; Family medical history; Female; Genetic aspects; Genetic counseling; Genetic diversity; Genetic screening; Genetic Testing; Genetic Variation; Genetics; Health aspects; Humans; Informed consent; Laboratories; Male; Medical laboratories; Medical research; Medicine, Experimental; Middle Aged; Pathogenic variants; Patient satisfaction; Patients; Quality management; Return of results; Smad3 protein; Thorax
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-021-00902-5

Disclosure of pathogenic variants to thoracic aortic dissection biobank participants was implemented. The impact and costs, including confirmatory genetic testing in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, were evaluated. We exome sequenced 240 cases with thoracic aortic dissection and 258 controls, then examined 11 aortopathy genes. Pathogenic variants in 6 aortopathy genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, and TGFBR2) were identified in 26 participants, representing 10.8% of the cohort (26/240). A second research sample was used to validate the initial findings. Mailed letters to participants disclosed that a potentially disease causing DNA alteration had been identified (neither the gene nor variant was disclosed). Participants were offered clinical genetic counseling and confirmatory genetic testing in a CLIA laboratory. Excluding 6 participants who were deceased or lost to follow-up, 20 participants received the disclosure letter, 10 of whom proceeded with genetic counseling, confirmatory genetic testing, and enrolled in a survey study. Participants reported satisfaction with the letter (4.2 ± 0.7) and genetic counseling (4.4 ± 0.4; [out of 5, respectively]). The psychosocial impact was characterized by low decisional regret (11.5 ± 11.6) and distress (16.0 ± 4.2, [out of 100, respectively]). The average cost for 26 participants was $400, including validation and sending letters. The average cost for those who received genetic counseling and CLIA laboratory confirmation was $605. Participants were satisfied with the return of clinically significant biobank genetic results and CLIA laboratory testing; however, the process required significant time and resources. These findings illustrate the trade-offs involved for researchers considering returning research genetic results.