Clinical Exome Sequencing: A Genetic Diagnostic Approach for Inherited Retinal Dystrophies
Pilar Barberán-Martínez1, Mar Balanzá1, Belén García-Bohórquez2
1Molecular, Cellular, and Genomic Biomedicine Group, Health Research Institute La Fe, Valencia, Spain; Programa de Doctorat en Biotecnologia, Universitat Politècnica de València (UPV), Valencia, Spain.
The Journal of Molecular Diagnostics : JMD
|January 7, 2026
Summary
Clinical exome sequencing identified genetic causes for 68.53% of inherited retinal dystrophy families, revealing novel variants and expanding gene associations for these rare vision disorders.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Inherited retinal dystrophies (IRDs) are rare, genetically diverse vision disorders with significant clinical variability.
- Accurate genetic diagnosis is crucial for understanding IRD pathogenesis and potential treatments.
Purpose of the Study:
- To evaluate the diagnostic yield of clinical exome sequencing (CES) in families with clinically diagnosed IRDs.
- To identify novel genetic variants and expand the spectrum of genes associated with IRDs.
Main Methods:
- Clinical exome sequencing (CES) was performed on 143 families with IRDs.
- Variant filtering and classification followed American College of Medical Genetics guidelines.
- Functional assays, including minigene analysis, were used to assess variant pathogenicity.
Main Results:
- A genetic diagnosis was achieved in 68.53% of the cohort, identifying 35 causative genes, notably ABCA4 and USH2A.
- 170 clinically relevant variants were found, with 45 (26.47%) being novel, predominantly missense variants.
- Aberrant splicing was confirmed for the ABCA4 c.1299A>G mutation; FAM161A and GUCY2D were newly associated with certain IRDs.
Conclusions:
- CES is an effective strategy for diagnosing IRDs, significantly increasing diagnostic yield.
- The study expands the known genetic landscape of IRDs, identifying novel variants and gene-disease associations.
- Findings contribute to a better understanding of IRD genetics and support the utility of comprehensive genetic testing.
