The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China

Jingying Wu; Xin Cheng; Duxin Ji; Huiwen Niu; Songquan Yao; Xukun Lv; Jianqiang Wang; Ziyi Li; Haoran Zheng; Yuwen Cao; Feixia Zhan; Mengyuan Zhang; Wotu Tian; Xiaojun Huang; Xinghua Luan; Li Cao

doi:10.1002/mds.29764

The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China

Mov Disord. 2024 Mar 11. doi: 10.1002/mds.29764. Online ahead of print.

Authors

Jingying Wu^{1

2}, Xin Cheng¹, Duxin Ji^{1

3}, Huiwen Niu⁴, Songquan Yao⁴, Xukun Lv⁴, Jianqiang Wang⁴, Ziyi Li¹, Haoran Zheng^{1

5}, Yuwen Cao¹, Feixia Zhan¹, Mengyuan Zhang^{1

5}, Wotu Tian¹, Xiaojun Huang¹, Xinghua Luan¹, Li Cao^{1

2

6}

Affiliations

¹ Department of Neurology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform, Shanghai, China.
³ Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China.
⁴ School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Neurology, The First Hospital Affiliated to Anhui University of Science & Technology, Huainan, China.
⁶ China Adult-Onset Leukoencephalopathy with Neuroaxonal Spheroids and Pigmented Glia Collaborative Group (CACG), Shanghai, China.

PMID: 38465843
DOI: 10.1002/mds.29764

Abstract

Background: Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated.

Objective: The objective of the study is to clarify the core features and influence factors of CRD patients in China.

Methods: Clinical and genetic-related data of CRD patients in China were collected. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations.

Results: A total of 103 patients were included, with a male-to-female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients.

Conclusions: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society.

Keywords: China; colony-stimulating factor 1 receptor; leukoencephalopathy; phenotype-genotype relationship; sex difference.

Abstract

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