Cascade testing after exome sequencing: Retrospective analysis of linked family data at 2 US laboratories.
Cascade screening
Cascade testing
Clinical laboratory
Exome sequencing
Familial testing
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
31
10
2022
revised:
16
02
2023
accepted:
22
02
2023
medline:
8
5
2023
pubmed:
1
3
2023
entrez:
28
2
2023
Statut:
ppublish
Résumé
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 a positive exome sequencing (ES) result in a population of probands with diverse clinical indications. We retrospectively reviewed administrative data from 2 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 on the basis of cascade testing completion. Among the 3723 positive ES results 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. Of the 426 relatives tested, 200 had a variant of interest detected (variant detection yield = 47.0%). In our real-world data analysis, a small proportion of probands with a positive ES result subsequently had relatives complete cascade testing at the same laboratory. However, approximately half of the tested relatives received a clinically significant result that could have implications for clinical management or reproductive planning. Additional research on ways to increase cascade testing uptake is warranted.
Identifiants
pubmed: 36852743
pii: S1098-3600(23)00831-6
doi: 10.1016/j.gim.2023.100818
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100818Subventions
Organisme : NHGRI NIH HHS
ID : K99 HG011491
Pays : United States
Informations de copyright
Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of Interest H.S.S. and H.S. declare no conflict of interest. J.S. and M.T. are salaried employees at Ambry Genetics, a Konica Minolta, Inc company. Baylor College of Medicine and Miraca Holdings Inc have formed a joint venture with shared ownership and governance of Baylor Genetics, which performs genetic testing and derives revenue. P.L. is an employee of Baylor College of Medicine and derives support through a professional services agreement with Baylor Genetics.