The strong effect of heterozygous mutations in CSF1R, resulting in severe progressive leukodystrophy and dramatically reduced microglia numbers, can be explained by a dominant-negative effect: all but a few causative genetic variants in ALSP patients are missense and affect one of the two tyrosine kinase domains (Konno et al., 2017). This evidence concerns the gene CSF1R and Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia.