Identification of a de novo splicing mutation in the CSF1R gene in a Chinese patient with hereditary diffuse leukoencephalopathy with spheroids.

Objective: To report a de novo splicing mutation in the CSF1R gene in a patient with hereditary diffuse leukoencephalopathy with spheroids (HDLS).

Methods: A 42-year-old Chinese woman with constant weakness on her left lower extremity was recruited in the current study. Detail medical history and clinical characteristics were reviewed. Brain magnetic resonance imaging (MRI), whole-exome sequencing, and Sanger sequencing were performed with bioinformatics analysis.

Results: The Chinese HDLS patient with no HDLS family history exhibited a de novo splicing mutation (c.1754-10 T > A) in the CSF1R gene. This mutation was located at the splice site of intron 12 and resulted in the skipping of exon 13 from the CSF1R mRNA. This finding constitutes the first de novo splicing mutation ever reported in HDLS. Furthermore, MRI abnormalities had been reported at least 6 months prior to the onset of the patient's clinical phenotype.

Conclusion: Our study indicates that the diagnosis of HDLS should be considered even in the absence of a family history and can help deepen the clinical and genetic understanding of HDLS.