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

Abstract

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.

Keywords: CSF1R; Hereditary diffuse leukoencephalopathy with spheroids (HDLS); Novel mutation.