SETX and proximal spinal muscular atrophy: Chronic low levels of SETX in SMA resulted in a higher ∼8-fold accumulation of R-loops in neurons compared to ∼2-fold in fibroblasts indicating a greater amount of DNA damage accumulation in neurons than in fibroblasts and suggesting a higher efficiency of DNA repair is required to prevent genomic instability and neurodegeneration.61 Because the motor neurons degenerate in SMA, these findings suggested a likely defect in the DNA repair mechanisms.