Friedreich ataxia (FRDA) is typically caused by homozygosity for an expanded GAA triplet-repeat in intron 1 of the FXN gene, which results in transcriptional deficiency via epigenetic silencing. Most patients are homozygous for alleles containing > 500 triplets, but a subset (~20%) have at least one expanded allele with 500 triplets, a significantly higher prevalence of unmethylated epialleles (median=9.8%) was observed in patients with at least one allele containing 20%) and later onset (>15y). The higher prevalence in mild FRDA of somatic FXN epialleles devoid of DNA methylation is consistent with variegated epigenetic silencing mediated by expanded triplet-repeats. The proportion of unsilenced somatic FXN genes is an unrecognized phenotypic determinant in FRDA, and has implications for the deployment of effective therapies.
Read the full article here
Please wait while your page loads ...
Archived in
2021 (120)