CASE REPORT article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1593964
A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report
Provisionally accepted
- 1Department of Neurology, Guizhou University of Traditional Chinese Medicine, Guizhou, China
- 2The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China
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Objective: We report a case of CSF1R-microglial encephalopathy associated with a rare intronic c.2654+1G>A mutation, featuring negative diffusion-weighted imaging (DWI) findings and a cerebrospinal fluid (CSF) biomarker profile indicative of Alzheimer's disease-related changes, and we explore the associations between genetic mutations, CSF biomarker alterations, and neuroimaging manifestations. Methods: This study documents the demographic data, detailed medical history, and clinical manifestations of a patient with CSF1R-microglial encephalopathy. The medical histories of some family members were collected, and the proband underwent whole-exome sequencing (WES) for diagnostic confirmation. Results: The patient, a 53-year-old woman, presented with early-onset cognitive decline, personality changes, and behavioral abnormalities. Neuropsychological testing revealed severe cognitive impairment, and the CSF biomarker profile suggested Alzheimer's disease-related changes. Cranial MRI showed bilateral, symmetric deep white matter changes, brain atrophy (including corpus callosum thinning), and low signal intensity on DWI. Family history revealed that 3 out of 19 individuals across four generations, including the proband, her aunt, and her sister, developed dementia and progressed to severe cognitive impairment rapidly. WES analysis revealed a heterozygous c.2654+1G>A variant in the CSF1R gene (NM_005211.3), confirming a diagnosis of CSF1R-microglial encephalopathy caused by a dominant autosomal mutation in exon 20 of the CSF1R gene. Conclusions: CSF1R-microglial encephalopathy is a progressive disorder with diverse early clinical presentations, making it prone to misdiagnosis and delayed treatment. This case suggests that, contrary to previous findings, negative DWI results should not exclude CSF1R-microglial encephalopathy. In addition, CSF biomarker profiles in patients with CSF1R-microglial encephalopathy may exhibit Alzheimer's disease-related changes. Early genetic testing is critical, and for genetically linked diseases, testing other family members can help ensure early diagnosis and intervention.
Keywords: CSF1R (Colony stimulating factor 1 receptor), Microglia, Dementia, gene, Magnetic Resonance Imaging
Received: 15 Mar 2025; Accepted: 06 Aug 2025.
Copyright: © 2025 Wu, Shi, Wang, Yang and Cai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jing Cai, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China
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