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

-related leukoencephalopathy, mainly caused by the mutation of the () 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 -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 -related leukoencephalopathy cases have been reported recently. In this study, we first report a 35-year-old woman with -related leukoencephalopathy carrying a novel missense mutation c.2463G >C (p.W821C) of . An extensive literature research was performed in order to better understand the broader genetic and clinical characteristics of -related leukoencephalopathy. A total of 147 patients with -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 -related leukoencephalopathy onset was 41.4 years. Typical clinical symptoms of -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 gene in patients with -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.