Disorders of nuclear-mitochondrial intergenomic signaling.

TitleDisorders of nuclear-mitochondrial intergenomic signaling.
Publication TypeJournal Article
Year of Publication2005
AuthorsSpinazzola, A, Zeviani, M
JournalGene
Volume354
Pagination162-8
Date Published2005 Jul 18
ISSN0378-1119
KeywordsCell Nucleus, DNA, Mitochondrial, Humans, Mitochondrial Diseases, Mitochondrial Proteins, Mutation, Nuclear Proteins, Phosphotransferases (Alcohol Group Acceptor), Signal Transduction, Thymidine Kinase, Thymidine Phosphorylase
Abstract

Depletion and multiple deletions of mitochondrial DNA (mtDNA) have been associated with a number of autosomal disorders classified as defects of nuclear-mitochondrial intergenomic signaling. The mendelian forms of progressive external ophthalmoplegia (PEO) are clinically and genetically heterogeneous disorders characterized by the accumulation of multiple deletions of mtDNA in postmitotic patient's tissues. Most of the autosomal dominant PEO (adPEO) families carry heterozygous mutations in either one of three genes: ANT1, Twinkle, and POLG1. Mutations in POLG1 can also cause autosomal recessive PEO (arPEO) and apparently sporadic cases. In addition, recessive POLG1 mutations are responsible for sensory-atactic neuropathy, dysarthria and ophthalmoplegia (SANDO), juvenile spino-cerebellar ataxia-epilepsy syndrome (SCAE) and Alpers-Huttenlocher hepatopathic poliodystrophy. Mutations in thymidine phosphorylase gene (TP) are linked to mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive disorder in which PEO is associated with gastrointestinal dysmotility and leukodystrophy. Finally, mitochondrial DNA depletion syndromes (MDS), defined by tissue-reduction in mtDNA copy number, have been linked to mutations in two genes involved in deoxyribonucleotide (dNTP) metabolism: thymidine kinase 2 (TK2) and deoxyguanosine kinase (DGUOK).

DOI10.1016/j.gene.2005.03.025
Alternate JournalGene
Citation Key10.1016/j.gene.2005.03.025
PubMed ID15921863
Grant ListGGP030039 / / Telethon / Italy