We noted that DNA damage repair defects in the setting of combined deficiency in DNA-PKcs and senataxin have also been observed in fibroblasts derived from patients with spinal muscular atrophy (SMA) and neurons from SMA mice, where the expression of senataxin and DNA-PKcs is compromised and elevated levels of endogenous DNA damage marked by γH2AX persist (65), raising the possibility that the kinase-helicase regulatory pathways described here likely function in genome maintenance in a broader context. This evidence concerns the gene SETX and proximal spinal muscular atrophy.