Clinical Exome Sequencing: A Genetic Diagnostic Approach for Inherited Retinal Dystrophies

Inherited retinal dystrophies (IRDs) represent a diverse group of rare pathologies affecting vision, with significant genetic and clinical variability. Clinical exome sequencing was performed on 143 families clinically diagnosed with IRDs. The obtained variants were filtered and classified according to the American College of Medical Genetics and Genomics guidelines. Overall, a genetic diagnosis was achieved for 68.53% of the families in the cohort; 35 causative genes were identified, predominantly ABCA4 and USH2A. A total of 170 clinically relevant variants were identified, 45 (26.47%) of which were novel, with missense variants being the most common type (40.59%). This study reported aberrant splicing generated by the ABCA4 (NM_000350.2): c.1299A>G mutation through the functional assay of a minigene. Furthermore, the genes FAM161A and GUCY2D were associated with IRDs that are not typically linked to these genes. Consequently, this study expands the current understanding of IRDs and supports the use of clinical exome sequencing as an effective strategy for the genetic diagnosis of these pathologies.