Next Generation Sequencing (NGS) technology offers an incredible opportunity for the rapid and relatively low-cost characterization of individual genomes, giving us a chance to make a substantial leap ahead in the molecular dissection of all mitochondrial disorders in humans.
This technology has led to the identification for the first time of pathological mutations in the RNASEH1 gene in six subjects from three unrelated families. This gene encodes the ribonuclease H1, a protein that is essential for life and it is present in both nucleus and mitochondria. While its role in the nucleus is unclear, it has previously been reported to be essential for the maintenance of the DNA present inside mitochondria or mitochondrial DNA (mtDNA). Affected tissues in these subjects not only showed lower amounts of mtDNA but also an accumulation of partly deleted mtDNA molecules. These alterations cause impaired energy production in the cells and therefore, lead to the disease. The clinical manifestations of affected individuals are chronic progressive external ophthalmoplegia (CPEO), a slowly progressive paralysis of the extraocular muscles, and exercise intolerance in early adulthood, followed by cerebellar and brain stem atrophy and a general weakness of the muscles affecting locomotion, eye movement, swallowing and speech.
The identification of a new mitochondrial disease gene not only provides valuable basic information about the biological function but also widens out knowledge on the mechanisms leading to disease and provide the basis for developing new and more effective therapies.
American Society for Human Genetics