Functional validation studies of genetic variants in mitochondrial and nuclear genes in patients with mitochondrial diseases

The objective of this project is to optimize the genetic diagnosis of mitochondrial patients by establishing a validation strategy with functional studies of new variants with unknown significance (VUS) that have been found in patients with mitochondrial diseases, in order to determine if they are the cause of the disease, and to achieve a genetic diagnosis. The strategy will include common and specific functional studies, depending on the type of mutation as well as the gene involved, in different cellular models as transmitochondrial cybrids for mtDNA variants and fibroblasts for nuclear genes. An algorithm of functional tests will be developed with the purpose to transfer it to the clinical diagnostic practice.