Pathogenic mitochondrial DNA mutations in protein-coding genes

✍ Scribed by Lee-Jun C. Wong

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 153 KB
• Volume: 36
• Category: Article
• ISSN: 0148-639X
• DOI: 10.1002/mus.20807

✦ Synopsis

Abstract

More than 200 disease‐related mitochondrial DNA (mtDNA) point mutations have been reported in the Mitomap (http://www.mitomap.org) database. These mutations can be divided into two groups: mutations affecting mitochondrial protein synthesis, including mutations in tRNA and rRNA genes; and mutations in protein‐encoding genes (mRNAs). This review focuses on mutations in mitochondrial genes that encode proteins. These mutations are involved in a broad spectrum of human diseases, including a variety of multisystem disorders as well as more tissue‐specific diseases such as isolated myopathy and Leber hereditary optic neuropathy (LHON). Because the mitochondrial genome contains a large number of apparently neutral polymorphisms that have little pathogenic significance, along with secondary homoplasmic mutations that do not have primary disease‐causing effect, the pathogenic role of all newly discovered mutations must be rigorously established. A scoring system has been applied to evaluate the pathogenicity of the mutations in mtDNA protein‐encoding genes and to review the predominant clinical features and the molecular characteristics of mutations in each mtDNA‐encoded respiratory chain complex. Muscle Nerve, 2007