Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.
Genet Med
; 23(9): 1689-1696, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-33976420
ABSTRACT
PURPOSE:
To evaluate the diagnostic yield and clinical relevance of clinical genome sequencing (cGS) as a first genetic test for patients with suspected monogenic disorders.METHODS:
We conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups standard-of-care genetic testing (SOC) only or SOC and cGS.RESULTS:
Two hundred four participants were enrolled, 202 were randomized to one of the intervention arms, and 99 received cGS. In total, cGS returned 16 molecular diagnoses that fully or partially explained the indication for testing in 16 individuals (16.2% of the cohort, 95% confidence interval [CI] 8.9-23.4%), which was not significantly different from SOC (18.2%, 95% CI 10.6-25.8%, P = 0.71). An additional eight molecular diagnoses reported by cGS had uncertain relevance to the participant's phenotype. Nevertheless, referring providers considered 20/24 total cGS molecular diagnoses (83%) to be explanatory for clinical features or worthy of additional workup.CONCLUSION:
cGS is technically suitable as a first genetic test. In our cohort, diagnostic yield was not significantly different from SOC. Further studies addressing other variant types and implementation challenges are needed to support feasibility and utility of broad-scale cGS adoption.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pruebas Genéticas
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Patología Molecular
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Risk_factors_studies
Límite:
Adult
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Child
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Humans
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos