MtDNA-maintenance defects: syndromes and genes.
A large group of mitochondrial disorders, ranging from early-onset pediatric encephalopathic syndromes to late-onset myopathy with chronic progressive external ophthalmoplegia (CPEOs), are inherited as Mendelian disorders characterized by disturbed mitochondrial DNA (mtDNA) maintenance. These errors of nuclear-mitochondrial intergenomic signaling may lead to mtDNA depletion, accumulation of mtDNA multiple deletions, or both, in critical tissues. The genes involved encode proteins belonging to at least three pathways: mtDNA replication and maintenance, nucleotide supply and balance, and mitochondrial dynamics and quality control. In most cases, allelic mutations in these genes may lead to profoundly different phenotypes associated with either mtDNA depletion or multiple deletions.
MRC-Mitochondrial Biology Unit, MRC MBU, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK.
Carlo
C
Viscomi
MRC-Mitochondrial Biology Unit, MRC MBU, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK. mdz21@mrc-mbu.cam.ac.uk.
Massimo
M
Zeviani
D000483:Alleles; D000818:Animals; D001706:Biopsy; D002467:Cell Nucleus / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000473:pathology*; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D009154:Mutation; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics*; D010641:Phenotype; D015398:Signal Transduction; D013577:Syndrome
D004272:DNA, Mitochondrial