MOLECULAR DIAGNOSIS OF INHERITED RETINAL DYSTROPHIES IN A COLOMBIAN POPULATION (DISRET-COLOMBIA)

Inherited retinal dystrophies (IRD) are a major cause of inherited blindness across the world. They are caused by the progressive deterioration or the early loss of retinal cells (1). IRD are clinically heterogeneous and vary widely in their severity, pathogenesis, manner of disease progression, inheritance pattern and age of onset (1). Worldwide, IRDs have an estimated prevalence of one in 3,000-5,000 (2). To date, more than 300 loci associated with retinal dystrophies have been identified (RetNet; update Mar 2021 https://sph.uth.edu/retnet/). In Colombia, few data are known about mutations and their frequencies in genes associated with IRD. The study of these genes is of great relevance for the genotyping of those affected and the subsequent counseling of their families. The identification of the disease-causing mutation in affected individuals enables an accurate diagnosis to be established, which contributes to better rehabilitation and empowerment for the affected individual. On the other hand, the identification of the mutations in the Colombian population allows us to provide frequencies that are unknown worldwide. Additionally, it opens up the possibility of studying their pathophysiology in the near future and thus being able to offer therapeutic options to individuals diagnosed with this highly disabling disease. Our research group has carried out important clinical and molecular work on visual and hearing diseases of genetic origin, including Retinitis Pigmentosa, but there is still a proportion of the population in which the mutation causing the disease has not been identified. From national brigades, we have identified a population of about 200 individuals unrelated to a diagnosis of RP or some other type of IRD. Of this population, we have 100 individuals who still do not have a molecular diagnosis. These individuals belonged to schools for the visually impaired. The purpose of this project is to identify IRD-causing mutations in a population of 100 affected individuals. To achieve this, we will perform a targeted exome analysis (Retinal Dystrophy panel) using next generation sequencing (NGS). This analysis will be carried out and sponsored by the Invitae Laboratory. Clarifying the molecular diagnosis of this population provides greater opportunities for rehabilitation of these patients. Studies have shown that molecular diagnosis is important to define certain types of therapies. Certain treatments have been reported to be effective depending on the genotype, implicated gene, or inheritance mechanism (Foundation Fighting blindness - http://www.blindness.org/retinitis-pigmentosa). Finally, in the near future and with the implementation of this technique, we will be able to clarify the diagnosis in our population with IRD, and establish a mutational panel typical of the Colombian population thanks to the data obtained in this and previous investigations.