Adult-onset leukoencephalopathies with vanishing white matter with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5
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Leukoencephalopathy with vanishing white matter (VWM) is a type of leukoencephalopathy with autosomal recessive inheritance. Magnetic resonance imaging (MRI) reveals diffuse leukoencephalopathy with lesions having cerebrospinal fluid (CSF)-like signals. The clinical presentations include progressive cerebellar ataxia, spasticity, and mental decline. The course is chronic progressive with episodes of rapid deterioration following a minor head trauma. Mutations in the five gene-encoding subunits of the translation initiation factor eIF2B, EIF2B1-5, have been identified as the causative mutations for VWM. Although the age at onset of VWM is usually 2–6 years, patients with adult onset have been described. All adult-onset cases except one have been found to be associated with mutations in EIF2B5 . We report cases of adult-onset VWM with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5, which showed decreased eIF2B activities.
A Japanese woman aged 56 who experienced...
KeywordsCerebellar Ataxia Homozygous Mutation Minor Head Trauma Homozygous Region Progressive Cerebellar Ataxia
This work was supported in part by KAKENHI (Grant-in-Aid for Scientific Research) on Priority Areas, Innovative Areas, Global COE Program for Chemical Biology of the Diseases, and Scientific Research (A) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a Grant-in-Aid for Research on Intractable Diseases and Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Welfare and Labour, Japan. CGP gratefully acknowledges the support from the UK Biotechnology and Biotechnology Research Council.
The experiments comply with the current laws of the country in which they were performed. The authors report no conflicts of interest.
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