Wu HongYan, Shi JingYu, Wang XiaoShan, Yang Mei, Cai Jing
Department of Neurology, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Department of Neurology, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Front Genet. 2025 Aug 15;16:1593964. doi: 10.3389/fgene.2025.1593964. eCollection 2025.
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.
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.
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 gene (NM_005211.3), confirming a diagnosis of CSF1R-microglial encephalopathy caused by a dominant autosomal mutation in exon 20 of the gene.
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.
我们报告一例与罕见的内含子c.2654 + 1G>A突变相关的CSF1R小胶质细胞性脑病病例，其特征为扩散加权成像（DWI）结果阴性以及脑脊液（CSF）生物标志物谱显示与阿尔茨海默病相关的变化，并且我们探讨基因突变、CSF生物标志物改变与神经影像学表现之间的关联。
本研究记录了一名CSF1R小胶质细胞性脑病患者的人口统计学数据、详细病史和临床表现。收集了一些家庭成员的病史，先证者接受了全外显子测序（WES）以确诊。
该患者为一名53岁女性，表现为早发性认知衰退、人格改变和行为异常。神经心理学测试显示严重认知障碍，CSF生物标志物谱提示与阿尔茨海默病相关的变化。头颅MRI显示双侧对称的深部白质改变、脑萎缩（包括胼胝体变薄）以及DWI上的低信号强度。家族史显示，在包括先证者、她的姑姑和她的妹妹在内的四代人中，19人中有3人患痴呆并迅速进展为严重认知障碍。WES分析显示该基因（NM_005211.3）存在杂合的c.2654 + 1G>A变异，证实诊断为由该基因第20外显子的显性常染色体突变引起的CSF1R小胶质细胞性脑病。
CSF1R小胶质细胞性脑病是一种进行性疾病，早期临床表现多样，容易误诊和延误治疗。该病例表明，与先前的发现相反，DWI结果阴性不应排除CSF1R小胶质细胞性脑病。此外，CSF1R小胶质细胞性脑病患者的CSF生物标志物谱可能显示与阿尔茨海默病相关的变化。早期基因检测至关重要，对于有遗传关联的疾病，检测其他家庭成员有助于确保早期诊断和干预。
