Furthermore, mutations in BRF1, encoding a subunit of TFIIIB specific to type 1 and type 2 promoters, cause a cerebellar–facial–dental syndrome (MIM no. 616202) with significant phenotype overlap with POLR3–HLD (9, 10), thus further suggesting that type 2 transcripts may be of particular importance for disease pathogenesis. This evidence concerns the gene BRF1 and leukodystrophy.