• Kearns–Sayre syndrome
• large scale rearrangement
• mitochondrial DNA
• mitochondrial disease
• mtDNA deletion

• ATP, adenosine triphosphate
• CK, creatine kinase
• COX, cytochrome c oxidase
• KSS, Kearns-Sayre syndrome
• mtDNA, mitochondrial DNA
• PEO, progressive external ophthalmoplegia
• RCS, revised Cambridge sequence

Mitochondrial disorders are clinical phenotypes associated with abnormalities of the terminal component of mitochondrial energy metabolism—that is, oxidative phosphorylation. Oxidative phosphorylation is carried out in the inner mitochondrial membrane by the four enzyme complexes (I–IV), of the respiratory chain plus the adenosine triphosphate (ATP) synthase complex (complex V). All these complexes, except complex II, which is entirely nucleus encoded, contain both nucleus and mitochondrion encoded subunits, and their biosynthesis also requires co-operation between the nuclear and mitochondrial genomes. Because of this dual genetic control, oxidative phosphorylation diseases can be due to mutations either in mitochondrial DNA (mtDNA) or nuclear DNA genes. Pathogenic mutations of mitochondrial DNA include either large scale rearrangements, which are usually sporadic, or point mutations and micro-rearrangements, which are usually transmitted through the maternal lineage. However, these concepts have recently been challenged by the identification of one family in which a de novo microdeletion in a mtDNA gene was detected in a patient’s mitochondrial genome, which had clearly been inherited from the proband’s father¹ and of a family with a mother to offspring transmission of a single mtDNA deletion.²

We present here a case of maternal transmission of a single heteroplasmic deleted mtDNA species in two subjects, both affected by Kearns-Sayre syndrome (KSS).