Novel MT-ND gene variants causing adult-onset mitochondrial disease and isolated Complex I deficiency

We describe the clinical, genetic and molecular investigations of two patients with adult-onset mitochondrial disease and
biochemical deficiencies in muscle involving complex I in isolation, both due to novel genetic variants in mitochondrial DNA
(mtDNA)-encoded structural subunits of this respiratory chain component. The study of patient tissues – specifically skeletal muscle –
was key in confirming the molecular diagnosis in both cases after many years pursuing different lines of investigation,
re-enforcing the importance of access to a diagnostic muscle biopsy, the clinically-relevant tissue, in proving the pathogenicity of
novel mtDNA variants identified by high-throughput, next-generation sequencing technologies. As such, we believe that our paper
would be of interest not only to those experts in the field of mitochondrial and metabolic genetic disease but also to the general
readership of the Journal.