Impact of integrated translational research on clinical exome sequencing.
clinical practice
diagnostic odyssey
genomics
undiagnosed disease
variants of uncertain significance
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:
03 2021
03 2021
Historique:
received:
01
07
2020
accepted:
01
10
2020
revised:
30
09
2020
pubmed:
5
11
2020
medline:
4
6
2021
entrez:
4
11
2020
Statut:
ppublish
Résumé
Exome sequencing often identifies pathogenic genetic variants in patients with undiagnosed diseases. Nevertheless, frequent findings of variants of uncertain significance necessitate additional efforts to establish causality before reaching a conclusive diagnosis. To provide comprehensive genomic testing to patients with undiagnosed disease, we established an Individualized Medicine Clinic, which offered clinical exome testing and included a Translational Omics Program (TOP) that provided variant curation, research activities, or research exome sequencing. From 2012 to 2018, 1101 unselected patients with undiagnosed diseases received exome testing. Outcomes were reviewed to assess impact of the TOP and patient characteristics on diagnostic rates through descriptive and multivariate analyses. The overall diagnostic yield was 24.9% (274 of 1101 patients), with 174 (15.8% of 1101) diagnosed on the basis of clinical exome sequencing alone. Four hundred twenty-three patients with nondiagnostic or without access to clinical exome sequencing were evaluated by the TOP, with 100 (9% of 1101) patients receiving a diagnosis, accounting for 36.5% of the diagnostic yield. The identification of a genetic diagnosis was influenced by the age at time of testing and the disease phenotype of the patient. Integration of translational research activities into clinical practice of a tertiary medical center can significantly increase the diagnostic yield of patients with undiagnosed disease.
Identifiants
pubmed: 33144682
doi: 10.1038/s41436-020-01005-9
pii: S1098-3600(21)04945-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
498-507Commentaires et corrections
Type : ErratumIn
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