Science News
from research organizations

RNASEH1 mutations impair mtDNA replication, cause adult-onset mitochondrial encephalomyopathy

Date:
June 26, 2015
Source:
MRC Mitochondrial Biology Unit
Summary:
Next Generation Sequencing (NGS) technology offers an incredible opportunity for the rapid and relatively low-cost characterization of individual genomes, giving us a chance to make a substantial leap ahead in the molecular dissection of all mitochondrial disorders in humans.
Share:
FULL STORY

Next Generation Sequencing (NGS) technology offers an incredible opportunity for the rapid and relatively low-cost characterization of individual genomes, giving us a chance to make a substantial leap ahead in the molecular dissection of all mitochondrial disorders in humans.

This technology has led to the identification for the first time of pathological mutations in the RNASEH1 gene in six subjects from three unrelated families. This gene encodes the ribonuclease H1, a protein that is essential for life and it is present in both nucleus and mitochondria. While its role in the nucleus is unclear, it has previously been reported to be essential for the maintenance of the DNA present inside mitochondria or mitochondrial DNA (mtDNA). Affected tissues in these subjects not only showed lower amounts of mtDNA but also an accumulation of partly deleted mtDNA molecules. These alterations cause impaired energy production in the cells and therefore, lead to the disease. The clinical manifestations of affected individuals are chronic progressive external ophthalmoplegia (CPEO), a slowly progressive paralysis of the extraocular muscles, and exercise intolerance in early adulthood, followed by cerebellar and brain stem atrophy and a general weakness of the muscles affecting locomotion, eye movement, swallowing and speech.

The identification of a new mitochondrial disease gene not only provides valuable basic information about the biological function but also widens out knowledge on the mechanisms leading to disease and provide the basis for developing new and more effective therapies.


Story Source:

Materials provided by MRC Mitochondrial Biology Unit. Note: Content may be edited for style and length.


Journal Reference:

  1. Aurelio Reyes, Laura Melchionda, Alessia Nasca, Franco Carrara, Eleonora Lamantea, Alice Zanolini, Costanza Lamperti, Mingyan Fang, Jianguo Zhang, Dario Ronchi, Sara Bonato, Gigliola Fagiolari, Maurizio Moggio, Daniele Ghezzi, Massimo Zeviani. RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy. The American Journal of Human Genetics, 2015; DOI: 10.1016/j.ajhg.2015.05.013

Cite This Page:

MRC Mitochondrial Biology Unit. "RNASEH1 mutations impair mtDNA replication, cause adult-onset mitochondrial encephalomyopathy." ScienceDaily. ScienceDaily, 26 June 2015. <www.sciencedaily.com/releases/2015/06/150626084259.htm>.
MRC Mitochondrial Biology Unit. (2015, June 26). RNASEH1 mutations impair mtDNA replication, cause adult-onset mitochondrial encephalomyopathy. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/06/150626084259.htm
MRC Mitochondrial Biology Unit. "RNASEH1 mutations impair mtDNA replication, cause adult-onset mitochondrial encephalomyopathy." ScienceDaily. www.sciencedaily.com/releases/2015/06/150626084259.htm (accessed May 23, 2017).

RELATED STORIES