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ABSTRACT
Purpose
Cascade testing, the process of testing a proband’s at-risk relatives, is integral
to realizing the full value of genomic sequencing. However, there is little empirical
evidence on the uptake of cascade testing after positive exome sequencing (ES) in
a population of probands with diverse clinical indications.
Methods
We retrospectively reviewed administrative data from two US clinical laboratories
that perform ES. For each proband with a positive ES result, we used linked family
data to describe the frequency of relatives’ cascade testing performed at the same
laboratory, variant detection yield of cascade tests, and characteristics of probands
and relatives categorized based on cascade testing completion.
Results
Among 3,723 positive ES across both laboratories, 426 relatives of 282 probands completed
cascade testing (uptake: 7.6%). An average of 1.5 relatives (SD 0.9) were tested per
proband. Among the 426 relatives tested, 200 had a variant of interest detected (variant
detection yield: 47.0%).
Conclusion
In our real-world data analysis, a small proportion of probands with a positive ES
subsequently had relatives complete cascade testing at the same laboratory. However,
approximately half of the relatives tested received a clinically significant result
that could have implications for clinical management or reproductive planning. Additional
research on ways to increase uptake is warranted.
Keywords
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Article info
Publication history
Accepted:
February 22,
2023
Received in revised form:
February 16,
2023
Received:
October 31,
2022
Publication stage
In Press Accepted ManuscriptFootnotes
Haley Streff has no conflicts of interest to disclose. Dr. Smith is supported by K99HG011491. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Julie Stefka and Meghan Towne are salaried employees at Ambry Genetics, a Konica Minolta company. Baylor College of Medicine (BCM) and Miraca Holdings Inc. have formed a joint venture with shared ownership and governance of Baylor Genetics (BG), which performs genetic testing and derives revenue. Dr. Liu is an employee of BCM and derives support through a professional services agreement with BG.
Identification
Copyright
© 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
