Clinician-led exome sequencing reanalysis boosts diagnosis of inherited retinal disease

Clinician-led reanalysis of exome sequencing (ES) data significantly improves the diagnostic yield for patients with inherited retinal disease (IRD), identifying additional genetic causes that were missed in initial genetic testing, according to a study.

A multicenter prospective cohort study conducted in Korea examined the efficacy of reanalyzing ES data to improve diagnostic yields in patients with IRDs. The study included 264 unrelated patients who underwent comprehensive ophthalmologic examinations and ES analyses. The reanalysis, conducted by IRD specialists, focused on detecting single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants.

Initial bioinformatic analysis diagnosed 166 patients (62.9%). However, clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, resulting in an 8.3-percentage point increase in the diagnostic rate.

New clinical information led to diagnoses in 4 patients. Structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients) were identified during reanalysis. Variants in 7 patients were observed but not reported during the initial analysis, while 15 patients had newly detected variants through reanalysis.

This research supports the growing recognition that reanalysis of genetic data, with updated clinical insights and comprehensive bioinformatics, is vital in the ongoing quest to diagnose and understand inherited retinal diseases more effectively.

Reference
Surl D, Won D, Lee ST, et al. Clinician-Driven Reanalysis of Exome Sequencing Data From Patients With Inherited Retinal Diseases. JAMA Netw Open. 2024;7(5):e2414198. doi: 10.1001/jamanetworkopen.2024.14198. PMID: 38819824; PMCID: PMC11143468.