Mitochondrial disorders are genetic conditions those faces great challenge in the accurate diagnoses due to extensive clinical heterogeneity associated with it. Mitochondria are the only cellular organelles containing their own genome and their functions are governed by both the nuclear and maternally inherited mitochondrial genomes, thus mitochondrial disease could follow all possible modes of inheritance adding to the complexity of diagnosis. Even though the prevalence of the mitochondrial disease has been studied in various parts of the world, the data regarding their prevalence in the Middle East population remains very limited. However, novel mitochondrial disease genes have been identified within the highly consanguineous Arab Middle East population, with the help of novel genetic technologies including the high throughput next-generation sequencing, leading to the identification of important founder mutations underlying several mitochondrial disorders. Furthermore, novel variants in mitochondrial disease genes help in expanding the spectrum of clinical phenotypes studied. The enrichment of reported phenotypes could enhance targeted gene panels leading to a rapid and precise genetic diagnosis facilitating genetic counseling. The aim of this review is to highlight the impact of next-generation sequencing on mitochondrial disease diagnosis in the Middle East population, particularly in identifying novel candidate genes and founder mutations. [JBCGenetics 2019; 2(1.000): 54-64]
