Sequence analysis of mitochondrial DNA in a new maternally inherited encephalomyopathy

A heteroplasmic insertion of a 9-bp tandem repeat element was detected in the mitochondrial DNA of the maternal members of a large family. The mutation was contained within the non-coding region between the genes specifying subunit II of cytochrome c oxidase and tR-NA(Lys). The proband and most of his maternal relatives were affected by a late-onset mitochondrial encephalomyopathy of variable severity, characterized by a unique combination of symptoms. Extensive screening of a large series of DNA samples, collected from unrelated normal individuals as well as patients affected by different neurological disorders, consistently failed to detect the 9-bp insertion, with two exceptions: a patient suffering from a syndrome virtually identical to that described in our original family and a child affected by bilateral striatal necrosis, a disorder which has been attributed to impairment of mitochondrial oxidative phosphorylation. These considerations suggest that the 9-bp insertion is pathogenic and that the region affected by the mutation may play a previously unsuspected functional role in mtDNA gene expression.