Mitochondrial DNA mutations and disease: It's the quantity that counts

Abstract

The mitochondriopathies represent true multifactorial disorders, and follow different genetic laws to the more familiar monogenic ‘nuclear’ diseases. These differences are very important to understanding the aetiology and clinical course of these disorders. The mitochondrial chromosome is very vulnerable to mutation, because of its exposure to a hostile environment and its relative lack of repair. The different mtDNA mutations can be classified according to their nature, and certain predictions made about the diseases produced. Point mutations in the genes coding for proteins produce hereditary disorders, which are generally restricted to certain tissues: most such mutations are associated with Leber's hereditary optic neuropathy. Point mutations in tRNA genes produce severe, multisystemic disorders which are also generally hereditary; they are always associated with heteroplasmy. All point mutations have exclusively maternal transmission. Deletions of mtDNA are generally somatic in origin, and it is not clear how frequently they can be transmitted. They are invariably heteroplasmic, and are frequently associated with tissue-specific disorders. Disorders produced by heteroplasmic mutations are frequently progressive once symptoms manifest, and are often vulnerable to metabolic and/or environmental triggers.

Key Words:

• mitochondria
• mtDNA
• mutations
• heteroplasmy
• multifactorial disease