Missense mutations in POLR3A, POLR3B and POLR1C causing POLR3-HLD are located throughout the three genes without clear hotspots (Wolf et al., 2014a; Gauquelin et al., 2019; Ramsay et al., 2020; Li G. et al., 2021; Girbig et al., 2021) and affect most major structural regions (Arimbasseri and Maraia, 2016). The gene discussed is POLR3B; the disease is leukodystrophy.