Background:
The most frequent mutation of Friedreich’s ataxia (FRDA) is the abnormal expansion of a GAA repeat located within the first intron of FXN gene. It’s known that the length of GAA is directly correlated with disease severity. The effect of mutation is a severe reduction of mRNA. Recently, a link among aberrant CpG methylation, chromatin organization and GAA repeat was proposed.

Methods:
In this study, using pyrosequencing technology, we have performed a quantitative analysis of the methylation status of 5 CpG sites located within the region upstream of GAA repeat, in 67 FRDA patients.

Read More: DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich’s ataxia patients

To assess the utility of urinary isoprostanes as markers of oxidative injury in Friedreich ataxia (FA), we compared levels of urinary F(2)-isoprostanes in patients with FA and healthy control subjects. Levels of urinary F(2)-isoprostanes in FA patients were not different from controls and were not significantly associated with age, GAA repeat length, disability level, or the use of antioxidants. Thus, urinary F(2)-isoprostanes are not a useful biomarker in FA.

(c) 2008 Movement Disorder Society.

Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation

There is no effective treatment for the cardiomyopathy of the most common autosomal recessive ataxia, Friedreich's ataxia (FA). The identification of potentially toxic mitochondrial (MIT) iron (Fe) deposits in FA suggests that Fe plays a role in its pathogenesis. This study used the muscle creatine kinase conditional frataxin (Fxn) knockout (mutant) mouse model that reproduces the classical traits associated with cardiomyopathy in FA. We examined the mechanisms responsible for the increased cardiac MIT Fe loading in mutants. Moreover, we explored the effect of Fe chelation on the pathogenesis of the cardiomyopathy. Our investigation showed that increased MIT Fe in the myocardium of mutants was due to marked transferrin Fe uptake, which was the result of enhanced transferrin receptor 1 expression.

Read More: The MCK mouse heart model of Friedreich's ataxia

Frataxin, a mitochondrial protein that is directly involved in regulating cellular iron homeostasis, has been suggested to serve as an iron chaperone during cellular Fe–S cluster biosynthesis. In humans, decreased amounts or impaired function of frataxin causes the autosomal recessive neurodegenerative disorder Friedreich’s ataxia. Cellular production of Fe–S clusters is accomplished by the Fe cofactor assembly platform enzymes Isu (eukaryotes) and IscU (prokaryotes). In this report, we have characterized the overall stability and iron binding properties of the Drosophila frataxin homologue (Dfh). Dfh is highly folded with secondary structural elements consistent with the structurally characterized frataxin orthologs.

Read More: Drosophila Frataxin: An Iron Chaperone during Cellular Fe–S Cluster Bioassembly