International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11615 - 11615

Опубликована: Окт. 29, 2024

Friedreich ataxia (FRDA) is the most common inherited ataxia, primarily impacting nervous system and heart. It characterized by GAA repeat expansion in FXN gene, leading to reduced mitochondrial frataxin levels. Previously, we described a family displaying two expanded alleles, not only proband affected late-onset FRDA but also younger asymptomatic sister. The molecular characterization of repeats showed that sister carried canonical uninterrupted expended repeats, whereas had compound heterozygous for an GAAGGA motif. Therefore, decided perform RNA sequencing (RNA-seq) on fibroblasts from both sisters order understand whether some genes and/or pathways might be differently involved occurrence clinical manifestation. transcriptomic analysis revealed 398 differentially expressed genes. Notably, TLR4, IL20RB, SLITRK5 were up-regulated, while TCF21 GRIN2A down-regulated, as validated qRT-PCR. Gene ontology (GO) enrichment network highlighted significant involvement immune response neuronal functions. Our results, particular, suggest TLR4 may contribute inflammation FRDA, SLITRK5, TCF21, dysregulation play roles disease pathogenesis. This study introduces new perspectives inflammatory developmental aspects offering potential targets therapeutic intervention.

Язык: Английский