The classic Friedreich's ataxia phenotype (95-98%) is due to a homozygous GAA triplet repeat expansion in intron 1 of the FXN gene (Figure 1(a)), which results in low
frataxin protein levels, whereas compound heterozygous (2-5%) individuals possess GAA trinucleotide repeat expansion on one allele and point mutation on the other allele, as seen in our patient (Figure 1(b)).
"Transplantation of wildtype mouse HSPCs essentially rescued FA-impacted cells," said Stephanie Cherqui, "
Frataxin expression was restored.
Cases were examined in terms of the existence of a
frataxin mutation for FA, the existence of ataxin 1, ataxin 2, and ataxin 3, and voltage-dependent P/Q type calcium channel alpha 1a subunit (CACNAIA) gene mutations for SCA types 1,2, 3, and 6.
Friedreich's ataxia (FRDA), an inherited, progressive neurodegenerative disease, is caused by a reduced expression of the mitochondrial iron-binding protein,
frataxin. To study the pathophysiological mechanism of how
frataxin deficiency causes the devastating disease, we created a cellular model of FRDA by stably knocking down
frataxin in glioma LN428 cell line.
Friedreich's ataxia is caused by a mutation in the
frataxin gene, which results in progressive neurologic and cardiac symptoms typically first appearing in childhood or during the teenage years.
Similarly, overexpression of
frataxin, a protein associated with Friedreich ataxia, stimulated oxidative metabolism and elevated mitochondrial membrane potential and ATP content in several colon cancer cell lines [138].
DNA methylation and histone modifications representative of silent chromatin have been observed around the expanded GAA-repeat in intron 1 of the
Frataxin gene that causes Friedreich's ataxia [9].
Friedreich's Ataxia (FA) is a progressive, multisystem, degenerative disorder caused by a reduction in
frataxin. FA is primarily associated with DNA Triplet Repeat Expansion (TRE) in gene.
"Induction of Oxidative Metabolism by Mitochondrial
Frataxin Inhibits Cancer Growth: Otto Warburg Revisited." (1) Researchers postulated that cancer cells exhibit multiple alterations in mitochondrial content, structure, function, and activity.
Friedreich's Ataxia is rare hereditary disease affecting 1 in 50,000 individuals of European descent caused by a mutation in a gene which encodes
frataxin, a protein essential for proper functioning of mitochondria, the energy pumps of the cell.