A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report
ObjectiveWe 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...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1593964/full |
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| author | HongYan Wu JingYu Shi XiaoShan Wang Mei Yang Jing Cai |
| author_facet | HongYan Wu JingYu Shi XiaoShan Wang Mei Yang Jing Cai |
| author_sort | HongYan Wu |
| collection | DOAJ |
| description | ObjectiveWe 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.MethodsThis 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.ResultsThe 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.ConclusionCSF1R-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. |
| format | Article |
| id | doaj-art-04976c04f88a4e40a7ac6f0c0101cb98 |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-04976c04f88a4e40a7ac6f0c0101cb982025-08-20T03:41:40ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-08-011610.3389/fgene.2025.15939641593964A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case reportHongYan Wu0JingYu Shi1XiaoShan Wang2Mei Yang3Jing Cai4Department of Neurology, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Neurology, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Neurology, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Neurology, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Neurology, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaObjectiveWe 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.MethodsThis 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.ResultsThe 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.ConclusionCSF1R-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.https://www.frontiersin.org/articles/10.3389/fgene.2025.1593964/fullCSF1R (colony stimulating factor 1 receptor)microgliadementiagenemagnetic resonance imaging |
| spellingShingle | HongYan Wu JingYu Shi XiaoShan Wang Mei Yang Jing Cai A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report Frontiers in Genetics CSF1R (colony stimulating factor 1 receptor) microglia dementia gene magnetic resonance imaging |
| title | A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report |
| title_full | A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report |
| title_fullStr | A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report |
| title_full_unstemmed | A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report |
| title_short | A rare intronic c.2654+1G>A mutation in CSF1R-microglial encephalopathy: a case report |
| title_sort | rare intronic c 2654 1g a mutation in csf1r microglial encephalopathy a case report |
| topic | CSF1R (colony stimulating factor 1 receptor) microglia dementia gene magnetic resonance imaging |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1593964/full |
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