Exploring the Genetic Causes of Non-syndromic Retinal Dystrophies in Qatar

Abstract

Background. Non-syndromic retinal dystrophies (RDs) are a set of degenerative retinal diseases that vary clinically and genetically. RDs comprise several overlapping disorders such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). RDs are a major cause of vision loss in young adults globally. RDs are genetically heterogeneous and to date, over 250 genes have been associated with the disease pathogenesis. Aim. This study aims to investigate the genetic basis of non-syndromic RDs in the population of Qatar and to assess the diagnostic yield of the different genetic tests available through a retrospective cohort study. Methods. A retrospective chart review was conducted to investigate the genetic basis of non-syndromic RDs in Qatar. Data were collected from physical and electronic medical records of patients seen at the Department of Adult and Pediatric Medical Genetics, at Hamad Medical Corporation between "2015" and "2022".

Results. Our study identified 49 eligible patients with a total of 55 variants in 32 RDs-related genes. Qatari patients contributed the most to the study (61.2%). Rod-dominated phenotypes accounted for half (51%) of hereditary retinal diseases in our study cohort. Out of the 49 cases, 38 were solved, where the genetic test identified causative variants explaining the patient’s phenotype. Whole exome sequencing and mitochondrial genome testing (WES Plus) was the most utilized test. In our study, the ABCA4 gene exhibited the highest number of causal variants, with four identified as pathogenic or likely pathogenic. Among these variants, the c.5882 G>A variant was the most frequently reported. Conclusions. In conclusion, certain genes have recurrent variations that are most likely the result of regional founder effects. The study also highlighted the patient’s preference for WES as first-tier genetic testing in non-syndromic RDs cases. Moreover, family segregation studies play a major role in identifying possible causative variants. The clinical implications of these findings hold promise for improving patient care and management in the field of non-syndromic RDs. More investigation in the geographical region is required before conclusive generalizations. This is the first study of its sort to be conducted in Qatar, and it lays the groundwork for additional research on the epidemiology and genetics of non-syndromic RDs in Qatar.