Two causative genes encoding the largest subunits of human RNA polymerase III (Pol III) -POLR3A and POLR3B- have been identified [8, 9] and mutations in these genes may cause four overlapping hypomyelinating leukodystrophy phenotypes: 1) tremor-ataxia with central hypomyelination or TACH; 2) 4H syndrome; 3) leukodystrophy with oligodontia (LO); 4) diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC) [6–10]. The gene discussed is POLR3B; the disease is leukodystrophy.