Diagnostic yield of genome sequencing for children with intellectual disability and developmental delay.

This retrospective analysis covers 666 children under 18 years whose genome sequencing (GS) was performed in a clinical diagnostic laboratory for intellectual disability (ID) or developmental delay. GS was positive in 31.1% of children (207/666) and the phenotype-specific yield for ID/developmental delay was 27.9% (186 children); it reached 35.3% (103/292) in children without known prior genetic testing. Of the 259 variants leading to a diagnosis, 7.7% (20/259) had limited to no coverage on exome sequencing. The authors see this as further support for GS as a first-tier test, in line with professional society recommendations.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The most useful figure is the 7.7% of diagnostic variants poorly covered by exome, which quantifies the specific gain of genome sequencing in a common indication. It is, however, a laboratory series with no head-to-head exome comparison in the same patients. The higher yield in children without prior testing argues for genome sequencing at the first work-up rather than at the end of the pathway.

Analysis by Dr Thibaut Benquey