Hereditary retinal dystrophies (HRD) are a group of progressive visual diseases characterized by pronounced heterogeneity including genetic heterogeneity, allelic heterogeneity as well as clinical heterogeneity influenced by mutations in over 200 genes. Consequently this genetic complexity contributes to considerable variation in clinical expression and overlap of symptoms of disease entities, all of which may hamper making an accurate clinical diagnosis. These obstacles tamper molecular diagnostics making it challenging to predict the gene likely to be mutated. On the contrary, establishing molecular diagnosis is vital for effective genetic counseling as well as risk assessment for further conceptions. Nonetheless, it will also help to predict the clinical course and aid disease management which is the central importance of patients’ professional and social lives. This study was conducted to investigate the relevance of genetic testing with respect to accurate clinical assessment. We report two families previously diagnosed with hereditary Retinitis Pigmentosa who have remained ambiguous upon advanced genetic testing.

Two families referred to the Genomic Research Center seeking genetic counseling. They were candidates for PGD and PND. Upon obtaining informed consent, peripheral blood samples were drawn from family members and genomic DNA was extracted. Next generation sequencing was performed for 138 genes known for susceptibility of eye diseases by next generation sequencing. Sanger sequencing was also performed to verify the identified variants.

No deleterious mutation was identified in the families.

This study highlights the heterogeneous nature of retinal disease and significance of meticulous clinical diagnosis for life style management of visually disabled patients. Despite the availability of conventional NGS panels, genetic pattern of the disease remains unknown. Whole exome sequencing is an option to uncover the genetic basis of hereditary retinal dystrophies. Therefore the amalgamation of precise clinical diagnosis and advanced genetic testing may overcome the mystery of the disease. It is anticipated that these approaches will contribute to minimizing the risk of hereditary retinal diseases in relevant Iranian families.