Document Detail

Adult-onset hereditary leukoencephalopathy: classification and molecular basis of the disorder.
MedLine Citation:
PMID:  23196628     Owner:  NLM     Status:  In-Data-Review    
Adult-onset leukoencephalopathy involving the white matter of the brain is a heterogeneous disorder that exhibits a wide range of clinical manifestations. Recent advances in molecular genetics enable gene-based diagnosis of some forms of adult-onset leukoencephalopathy. In this review, the classification of adult-onset leukoencephalopathy based on molecular genetic findings is proposed. The autosomal dominant forms of adult-onset leukoencephalopathy include hereditary diffuse leukoencephalopathy with spheroids (HDLS), autosomal dominant adult-onset leukoencephalopathy (ALDL), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Alexander disease. The autosomal recessive forms of adult-onset leukoencephalopathy include cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), vanishing white matter (VWM) with leukoencephalopathy, Nasu-Hakola disease, and metachromatic leukodystrophy (MDL). X-chromosome-linked disorders include fragile X-associated tremor and ataxia syndrome (FXTAS) and adrenoleukodystrophy (ALD). Identification of the genes responsible for adult-onset leukoencephalopathy provides an important clue for elucidation of molecular pathophysiology underlying white matter disorders. One example is the identification of mutations in colony stimulating factor 1 receptor (CSF-1R) in patients with HDLS. Missense and splice site mutations have been found in the tyrosine kinase domain of CSF-1R. CSF-1R is highly expressed in microglia in the brain. It has been demonstrated that mice depleted of CSF-1R exhibit loss of microglia in the brain. In addition, stimulation of IL-34, a ligand of CSF-1R, induces proliferation and activation of microglia. These findings raise an intriguing possibility that dysfunction of microglia may play a role in the pathogenesis of white matter lesions occurring in patients with HDLS.
Takeshi Ikeuchi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Rinshō shinkeigaku = Clinical neurology     Volume:  52     ISSN:  1882-0654     ISO Abbreviation:  Rinsho Shinkeigaku     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417466     Medline TA:  Rinsho Shinkeigaku     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1386-9     Citation Subset:  IM    
Department of Neurology, Brain Research Institute, Niigata University.
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