Document Detail

The molecular and cellular defects underlying Pelizaeus-Merzbacher disease.
MedLine Citation:
PMID:  18485258     Owner:  NLM     Status:  MEDLINE    
Pelizaeus-Merzbacher disease (PMD) is a recessive X-linked dysmyelinating disorder of the central nervous system (CNS). The most frequent cause of PMD is a genomic duplication of chromosome Xq22 including the region encoding the dosage-sensitive proteolipid protein 1 (PLP1) gene. The PLP1 duplications are heterogeneous in size, unlike duplications causing many other genomic disorders, and arise by a distinct molecular mechanism. Other causes of PMD include PLP1 deletions, triplications and point mutations. Mutations in the PLP1 gene can also give rise to spastic paraplegia type 2 (SPG2), an allelic form of the disease. Thus, there is a spectrum of CNS disorder from mild SPG2 to severe connatal PMD. PLP1 encodes a major protein in CNS myelin and is abundantly expressed in oligodendrocytes, the myelinating cells of the CNS. Significant advances in our understanding of PMD have been achieved by investigating mutant PLP1 in PMD patients, animal models and in vitro studies. How the different PLP1 mutations and dosage effects give rise to PMD is being revealed. Interestingly, the underlying causes of pathogenesis are distinct for each of the different genetic abnormalities. This article reviews the genetics of PMD and summarises the current knowledge of causative molecular and cellular mechanisms.
Karen J Woodward
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2008-05-19
Journal Detail:
Title:  Expert reviews in molecular medicine     Volume:  10     ISSN:  1462-3994     ISO Abbreviation:  Expert Rev Mol Med     Publication Date:  2008  
Date Detail:
Created Date:  2008-05-19     Completed Date:  2008-07-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100939725     Medline TA:  Expert Rev Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  e14     Citation Subset:  IM    
Western Diagnostic Pathology, 74 McCoy Street, Myaree, WA 6154, Australia.
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MeSH Terms
Chromosomes, Human, X
Gene Deletion
Gene Duplication
Myelin Proteins / genetics,  physiology
Myelin Proteolipid Protein / chemistry,  genetics*,  physiology
Myelin Sheath / physiology
Pelizaeus-Merzbacher Disease / genetics*,  physiopathology
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Myelin Proteins; 0/Myelin Proteolipid Protein; 0/PLP1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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