LAUSR

Significance Here we demonstrate a previously unreported class of mitochondrial disease originating from the incompatibility of common mtDNA variants. Until now, clinical evaluation of the mitochondrial DNA only assessed the frequency of individual variants, and common variants were considered nonpathogenic. Our findings emphasize that common mtDNA variants can cause mitochondrial disease when arising on an uncommon mtDNA background. Thus, idiopathic primary mitochondrial disease patients should be checked for novel combinations of otherwise common variants which may contribute to the etiology of the disorder.