Differential gene expression in whole blood of Friedreich's ataxia patients. (A) Demographic breakdown of the participants, featuring sex- and age-matched samples used for the analysis. GAA1 and GAA2 lengths represent the number of GAA triplet repeat expansions in the first and second alleles, respectively, of the FXN gene, which are characteristic of Friedreich's ataxia. (B) A heat map representing significant gene up- and downregulation (depicted in rows) in whole blood from Friedreich's ataxia patients (n = 72), carriers (n = 68) and controls (n = 43), sourced from GEO data set GSE102008. In the heatmap, intensities of red (indicating gene upregulation) and blue (indicating gene downregulation) correspond to the respective levels of gene expression changes. (C) A heat map showing the top nine differentially expressed genes in Friedreich's ataxia patient's whole blood, selected for subsequent validation. (D) Preliminary screening of expression levels of candidate genes in the whole blood of FRDAkd mice, normalized to Hprt1. Expression levels were measured post-treatment with dox (Fxn knockdown) from Week 0 to Week 6 using RT-qPCR analyses. The individual circles represent data points from each animal, corresponding to the expression level of each candidate gene at 0, 2, 3 and 6 weeks post-Fxn knockdown. The up- and downregulation of these genes, as a result of dox-induced Fxn knockdown, are denoted by positive and negative signals, respectively. Sample size ranges from N = 3 to N = 5. Statistical analyses were performed using a one-way ANOVA and Welch's t-test. Data are presented as mean ± SEM. Significance is indicated as follows: *P ≤ 0.05, **P ≤ 0.01 and ***P ≤ 0.001.