Similarly, if reduced DNA 5′-kinase activity is a cause of cerebellar ataxia and neurodegeneration in PNKP-mutated disease our results implicate SSBs arising from abortive TOP1 activity in AOA4 and CMT2B2, because this is a major source of DNA breaks with 5′-hydroxyl termini. The gene discussed is TOP1; the disease is aceruloplasminemia.