A Novel Missense Mutation of the CSF1R Gene Causes Incurable CSF1R-Related Leukoencephalopathy: Case Report and Review of Literature

• Main Authors: Chen J, Luo S, Li N, Li H, Han J, Ling L
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-12-01
• Series: International Journal of General Medicine
• Subjects: csf1r-related leukoencephalopathy; clinical symptoms; csf1r
• Online Access: https://www.dovepress.com/a-novel-missense-mutation-of-the-csf1r-gene-causes-incurable-csf1r-rel-peer-reviewed-article-IJGM

Jie Chen,1 Shiying Luo,1 Ning Li,1 Huimin Li,1 Jinming Han,2 Li Ling1 1Department of Neurology, Affiliated Hospital of Hebei University, Baoding, People’s Republic of China; 2Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenCorrespondence: Li LingDepartment of Neurology, Affiliated Hospital of Hebei University, Baoding, People’s Republic of ChinaEmail [e-mail] HanDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenEmail [e-mail]: CSF1R-related leukoencephalopathy, mainly caused by the mutation of the colony stimulating factor 1 receptor (CSF1R) gene on chromosome 5, is an underestimated neurological disease typically presenting as early-onset cognitive decline and personality changes. Currently, there is no specific treatment for CSF1R-related leukoencephalopathy. Most clinicians failed to recognize this disease during an early disease stage, leading to a high rate of misdiagnosis. Although rare, an increasing amount of CSF1R-related leukoencephalopathy cases have been reported recently. In this study, we first report a 35-year-old woman with CSF1R-related leukoencephalopathy carrying a novel missense mutation c.2463G >C (p.W821C) of CSF1R. An extensive literature research was performed in order to better understand the broader genetic and clinical characteristics of CSF1R-related leukoencephalopathy. A total of 147 patients with CSF1R-related leukoencephalopathy confirmed either by the genetic test or brain biopsy were identified. Among them, 49 patients were sporadic, and the rest of individuals had a family history originating from 46 different families. Our study indicated that the average age of CSF1R-related leukoencephalopathy onset was 41.4 years. Typical clinical symptoms of CSF1R-related leukoencephalopathy include cognitive decline, movement disorders, behavior changes and mental disorders. Genetic studies have reported 93 missense mutations, 13 splicing mutations, 6 deletion/insertion mutations, 1 code shift mutation and 1 nonsense mutation of the CSF1R gene in patients with CSF1R-related leukoencephalopathy. Early genetic detection and brain biopsy would be helpful for a confirmed diagnosis, and more translational studies are needed to combat this devastating disease.Keywords: CSF1R-related leukoencephalopathy, clinical symptoms, CSF1R