Progressive external ophthalmoplegia and multiple mitochondrial DNA deletions.
Progressive external ophthalmoplegia (PEO) with secondary accumulation of multiple deletions of mitochondrial DNA (mtDNA) clinically resembles disorders due to primary mutations of mtDNA but follows a Mendelian inheritance pattern. The disorder belongs to an interesting group of diseases in which both the nuclear and the mitochondrial genome are involved in the pathology. Both autosomal dominant (adPEO) and recessive (arPEO) variants of this disorder occur. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients may have multiple mtDNA deletions and/or depletion of mtDNA. Recent reports of mutations in Thymidine Phosphorylase in MNGIE, and of mutations in adenine nucleotide translocator (ANT1), Twinkle and mitochondrial DNA polymerase gamma (POLG) in adPEO, have lead to new insights in the pathogenesis of these disorders of mtDNA maintenance. We also identified POLG mutations in two families with arPEO, which underlines the crucial role of the mtDNA replication machinery for mtDNA maintenance.
Van Goethem
Gert
G
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB-8), University of Antwerp (UIA). vgoethge@uia.ua.ac.be
Martin
Jean-Jacques
JJ
Van Broeckhoven
Christine
C
D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009801:Oculomotor Muscles / Q000473:pathology / Q000503:physiopathology*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase