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

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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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors are thankful to the patients and their families for their participation in the present study.

Funding

This work was supported by the National Key R&D Program of China (grant numbers 2017YFC0907704, 2017YFC0907705) and the Department of Science and Technology of Sichuan Province (grant number 2020YFS0219).

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Author notes

  1. Qin Du and Minjin Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, West China Hospital, Sichuan University, Guo Xuexiang #37, Chengdu, 610041, China

    Qin Du & Hongyu Zhou

  2. Department of Laboratory Medicine, West China Hospital, Sichuan University, Guo Xuexiang #37, Chengdu, 610041, China

    Minjin Wang

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  1. Qin Du
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  2. Minjin Wang
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  3. Hongyu Zhou
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Correspondence to Hongyu Zhou.

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The authors declare no competing interests.

Ethical approval

This study was approved by the Ethics Committee of Sichuan University. Written informed consent was obtained from all individual participants included in the study.

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Du, Q., Wang, M. & Zhou, H. A novel mutation in CSF1R associated with hereditary diffuse leukoencephalopathy with spheroids. Neurol Sci 43, 411–417 (2022). https://doi.org/10.1007/s10072-021-05296-x

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