Leigh Map: A Novel Computational Diagnostic Resource for Mitochondrial Disease

in Annals of Neurology (2017)

Mitochondrial disorders are amongst the most severe metabolic disorders and are beset by genetic, biochemical, and clinical heterogeneity. Variation between individuals and poor understanding of disease ... [more ▼]

Mitochondrial disorders are amongst the most severe metabolic disorders and are beset by genetic, biochemical, and clinical heterogeneity. Variation between individuals and poor understanding of disease pathophysiology pose significant diagnostic challenges. We present a novel interactive computational network, the Leigh Map, cataloguing >1700 gene-to-phenotype interactions in Leigh syndrome, the most common and genetically heterogeneous mitochondrial disorder. Blinded validation of the Leigh Map yielded an 80% success rate in correct identification of causative genes. We conclude that the Leigh Map is an efficacious resource that, in combination with whole-exome sequencing, can be utilized as a novel diagnostic resource for mitochondrial disease. [less ▲]