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

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare, autosomal-dominant neurological disorder.
• It is characterized by progressive cognitive decline and motor dysfunction.
• High penetrance is a notable feature of HDLS.

Purpose of the Study:

• To identify the genetic cause of HDLS in a Chinese family.
• To describe a new variant of the colony stimulating factor-1 receptor (CSF1R) gene associated with HDLS.

Main Methods:

• Clinical evaluations including physical examinations and laboratory tests.
• Neuroimaging studies such as brain MRI.
• Whole-exome sequencing for genetic analysis.

Main Results:

• Three family members presented with typical HDLS symptoms, including cognitive and motor deficits.
• A heterozygous missense mutation (c.2264T>C, p.L755P) in the CSF1R gene was identified.
• This mutation segregated with the HDLS phenotype in an autosomal-dominant inheritance pattern.

Conclusions:

• A novel CSF1R gene mutation, p.L755P, is identified in a Chinese family with autosomal-dominant HDLS.
• This discovery broadens the genetic landscape of CSF1R-associated HDLS.
• The findings contribute to understanding the genetic basis of this rare disorder.