LETTER TO JMG

Identical large scale rearrangement of mitochondrial DNA causes Kearns-Sayre syndrome in a mother and her son

G Puoti¹, F Carrara², S Sampaolo¹, M De Caro³, C M Vincitorio¹, F Invernizzi², M Zeviani²

¹ Department of Neurosciences, School of Medicine, Federico II State University, Naples, Italy
² Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Center for the Study of Children’s Mitochondrial Disorders, National Neurological Institute C. Besta, Milan, Italy
³ Division of Anesthesiology, Public General Hospital, Mercato San Severino (SA), Italy

Correspondence to:
Correspondence to:
Dr M Zeviani
Division of Molecular Neurogenetics, National Neurological Institute Carlo Besta, via Temolo 4, 20126 Milan, Italy; zeviani@tin.it

Keywords: Kearns–Sayre syndrome; large scale rearrangement; mitochondrial DNA; mitochondrial disease; mtDNA deletion

Abbreviations: 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

The first 150 words of the full text of this article appear below.

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 . . . [Full text of this article]

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