Mitochondrial DNA Defects: A Widening Clinical Spectrum of Disorders

Abstract

1. Mitochondrial DNA has a number of interesting properties including maternal transmission, the ability to replicate in post-mitotic cells, a high mutation rate and an extremely compact molecular architecture with no introns and no large non-coding sequences. 2. Point mutations, deletions and duplications of mitochondrial DNA may occur. Mitochondrial DNA defects may co-exist with wild-type sequence within a cell (heteroplasmy). The level of heteroplasmy may vary in different tissues within the same individual (segregative replication). 3. A number of neurological disorders are characterized by morphological and biochemical mitochondrial defects. It is now clear that mitochondrial DNA mutations underlie these conditions although there is not always a clear correlation between a particular mutation and clinical presentation. 4. Mitochondrial DNA defects, particularly deletions, accumulate in senescent tissue and studies have been performed with the aim of linking such somatic mutations with degenerative disorders. 5. Recently mitochondrial DNA mutations have been implicated in a wider range of clinical disorders including diabetes and nerve deafness. 6. Nuclear gene defects may result in mitochondrial disorders by predisposing to multiple mitochondrial DNA deletions or quantitative depletions of mitochondrial DNA content.