A novel mutation in CSF1R associated with hereditary diffuse leukoencephalopathy with spheroids

Background Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal-dominant disorder with high penetrance characterized by progressive cognitive and motor dysfunction. The objective of the study was to describe a new variant of the colony stimulating factor-1 receptor ( CSF1R ) gene causing HDLS in a Chinese family. Methods Physical examinations, laboratory tests, structural neuroimaging studies, and whole-exome sequence analysis were carried out. Results Three patients in this family exhibited typical manifestations of HDLS, including progressive cognitive impairment, language and motor dysfunctions, and urinary and bowel incontinence. Genetic analysis identified a heterozygous missense mutation (c.2264T>C, p.L755P) in exon 17 of the CSF1R gene that cosegregated with the HDLS phenotype in an autosomal-dominant pattern. Brain MRI of the proband and her father showed diffuse white matter changes. The proband’s 10-year-old son, a gene carrier, remains clinically asymptomatic at present. Conclusions Our findings identify a novel missense mutation, p.L755P, in the CSF1R gene within a Chinese family with autosomal-dominant HDLS and broaden the genetic spectrum of CSF1R -associated HDLS.