OLIG2 and leukodystrophy: Although we cannot yet say with certainty that this is true in POLR3-HLD, in the only existing study quantifying oligodendrocyte-specific immunohistochemistry in a patient, OLIG2+ cells were reduced in number by 70–99% when compared to a control, depending on the brain region.11 Therefore, our current understanding of POLR3-HLD pathophysiology indicates that putative interventions should be targeted to early stages of the oligodendrocyte lineage in order to produce therapeutic benefit, in line with recently published hypotheses by Perrier and colleagues.77