Hereditary diffuse leukoencephalopathy with spheroids is an adult-onset neurodegenerative disorder characterized by behavioral, cognitive, and motor changes. The disorder is cased by mutation in the colony-stimulating factor-1 receptor gene (CSF1R, Rademakers R, 2011; PMID: 22197934). The progression of the disease is very rapid, as patients usually die few years because of dementia. However, patients that survive in adult age are described: Kinoshita M et al recently reported about a 51-year old woman who gradually developed a decline in cognitive functions and whose relatives were diagnosed as having dementia in their forties to sixties (PMID: 22503135). From the etiopathogenetic side, it is interesting tho highlight that Langerhans cells and microglia develop from embryonic myeloid precursor cells of the epidermis and central nervous system before birth and that they are present in CSF1-deficient mice but absent from CSF1R-deficient mice (Wang Y et al, 2012, PMID: 22729249). Thus, the CSF1 receptor regulates CNS microglial development. Other interesting evidence of the role of CSF1R and its ligand (IL-34) has been reported by Nandi S et al (2012), who found that CSF1R-deficient mice have smaller brains, expansion of lateral ventricle size, atrophy of the olfactory bulb and a failure of midline crossing of callosal axons (PMID: 22542597). The disorder is autosomal dominant.
FACTS
The CSF1R gene spans about 64.1 KB and includes 22 exons. It is located on 5q32.
References: see text.
FACTS
The CSF1R gene spans about 64.1 KB and includes 22 exons. It is located on 5q32.
References: see text.
