Summary
Inherited retinal dystrophies (IRDs) are genetically and phenotypically heterogeneous, and early molecular diagnosis is critical for management and access to emerging therapies. We retrospectively analyzed 1,612 pediatric patients (age 0–12) tested with a multigene panel. Analysis included all protein-coding exons, clinically relevant noncoding variants, the mitochondrial genome, and copy number variant (CNV) detection. Pathogenic or likely pathogenic variant(s) consistent with phenotype were identified in 56.2% of cases (906/1612), spanning 114 genes. Five genes (ABCA4, RS1, CNGB3, RPGR, CEP290) accounted for 37.3% of diagnoses. CNVs contributed to 4.4% of diagnoses, with 39.4% being 1 or 2 exons in size. Noncoding variants explained 10.6% of cases, with 26.3% of these located >10 bp from exon-intron boundaries. Mitochondrial variants were responsible for 3 diagnoses. These findings underscore the value of comprehensive multi-gene panel testing that included CNV analysis, clinically relevant noncoding variants, and mitochondrial analysis to maximize diagnostic yield in pediatric IRDs.
Authors:
Kimberly Gall, Iker Sanchez Navarro, Julie Hathaway, Alicia Scocchia, Kati Kämpjärvi, Johanna Känsäkoski, Pernilla von Nandelstadh, Marta Gandia, Sanna Vattulainen-Collanus, Ka-Yan Mak, Mari-Liis Lukke, Sonia Casanovas, Laura Sarantaus, Hann Västinsalo, Inka Saarinen, Sari Tuupanen, Juha Koskenvuo