[HTML][HTML] A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders
Genetics in medicine, 2016•nature.com
Purpose: To prospectively evaluate the diagnostic and clinical utility of singleton whole-
exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease.
Methods: Singleton WES was performed as a first-tier sequencing test in infants recruited
from a single pediatric tertiary center. This occurred in parallel with standard investigations,
including single-or multigene panel sequencing when clinically indicated. The diagnosis
rate, clinical utility, and impact on management of singleton WES were evaluated. Results …
exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease.
Methods: Singleton WES was performed as a first-tier sequencing test in infants recruited
from a single pediatric tertiary center. This occurred in parallel with standard investigations,
including single-or multigene panel sequencing when clinically indicated. The diagnosis
rate, clinical utility, and impact on management of singleton WES were evaluated. Results …
Abstract
Purpose:
To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease.
Methods:
Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single-or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated.
Results:
Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies.
Conclusions:
This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.
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