Unveiling ocular developmental disorders through short-read whole-genome sequencing.

Short-read whole-genome sequencing (WGS) applied to developmental eye malformations unresolved by panels or CGH-array.

Short-read whole-genome sequencing (WGS) in a cohort of 100 families with ocular developmental disorders (microphthalmia-anophthalmia spectrum, coloboma, anterior segment dysgenesis, congenital cataract, foveal hypoplasia). None had a diagnosis despite prior targeted NGS panels and/or CGH-array. WGS identified a (likely) pathogenic variant in 18 patients and candidate variants in 9 more. Notably, fourteen of these variants would have been missed by conventional panels or CGH-array, underscoring the broader diagnostic scope of WGS.

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

A clear demonstration of WGS yield where panels fail: 14 of the diagnostic variants were beyond the reach of a targeted panel or CGH-array. This aligns with the exome/genome trajectory — a single test capturing SNVs, CNVs and regions not covered by panels. The yield (18/100) is solid for previously negative cases, though the cohort remains single-centre.

Analysis by Dr Thibaut Benquey