Anu Suomalainen M.D., Ph.D., is visiting scientist at the Montreal Neurological Institute, with interests including nuclear genes controlling mtDNA maintenance and pathogenetic mechanisms underlying autosomal dominant progressive external ophthalmoplegia with multiple mtDNA deletions. She is affiliated with the National Public Health Institute, Helsinki, Finland.
Diseases caused by nuclear genes affecting mtDNA stability
Article first published online: 22 JUN 2001
Copyright © 2001 Wiley-Liss, Inc.
American Journal of Medical Genetics
Special Issue: Mitochondrial Diseases
Volume 106, Issue 1, pages 53–61, Spring 2001
How to Cite
Suomalainen, A. and Kaukonen, J. (2001), Diseases caused by nuclear genes affecting mtDNA stability. Am. J. Med. Genet., 106: 53–61. doi: 10.1002/ajmg.1379
- Issue published online: 23 OCT 2002
- Article first published online: 22 JUN 2001
- Sigrid Juselius Foundation
- Finnish Cultural Foundation
- multiple mtDNA deletions;
- progressive external ophthalmoplegia;
- mitochondrial disease;
Diseases caused by nuclear genes that affect mitochondrial DNA (mtDNA) stability are an interesting group of mitochondrial disorders, involving both cellular genomes. In these disorders, a primary nuclear gene defect causes secondary mtDNA loss or deletion formation, which leads to tissue dysfunction. Therefore, the diseases clinically resemble those caused by mtDNA mutations, but follow a Mendelian inheritance pattern. Several clinical entities associated with multiple mtDNA deletions have been characterized, the most frequently described being autosomal dominant progressive external ophthalmoplegia (adPEO). MtDNA depletion syndrome (MDS) is a severe disease of childhood, in which tissue-specific loss of mtDNA is seen. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients may have multiple mtDNA deletions and/or mtDNA depletion. Recent reports of thymidine phosphorylase mutations in MNGIE and adenine nucleotide translocator mutations in adPEO have given new insights into the mechanisms of mtDNA maintenance in mammals. The common mechanism underlying both of these gene defects could be disturbed mitochondrial nucleoside pools, the building blocks of mtDNA. Future studies on MNGIE and adPEO pathogenesis, and identification of additional gene defects in adPEO and MDS will provide further understanding about the mammalian mtDNA maintenance and the crosstalk between the nuclear and mitochondrial genomes. © 2001 Wiley-Liss, Inc.