title: Pathogenic mitochondrial DNA mutations in protein-coding genes.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB2015, Houston, Texas 77030, USA. ljwong@bcm.edu
authors.forename: Lee-Jun C
authors.initials: LJ
authors.lastname: Wong
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D045303:Cytochromes b / Q000235:genetics; D004272:DNA, Mitochondrial / Q000737:chemistry*; D006801:Humans; D007888:Leigh Disease / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000235:genetics*; D017240:Mitochondrial Myopathies / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases; D009154:Mutation; D010809:Physical Fitness
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D045303:Cytochromes b; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; C020439:oligomycin sensitivity-conferring protein