In 2012 Rademakers et al. reported fourteen families with HDLS in whom a combination of linkage analysis and exome sequencing had revealed mutations in the tyrosine kinase domain of CSF1R. Functional studies suggested that the mutations affect the kinase activity of the protein, probably altering the phosphorylation of downstream targets. This evidence concerns the gene CSF1R and Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia.