Duplication of proteolipid protein gene: A possible major cause of Pelizaeus-Merzbacher disease

Wang, Pen-Jung; Hwu, Wuh‐Liang; Lee, Wang-Tso; Wang, Tso‐Ren; Shen, Yu-Zen

doi:10.1016/s0887-8994(97)00088-x

Cited by 27 publications

(16 citation statements)

References 14 publications

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“…The paradox was resolved when Inoue and colleagues [88] recognized that submicroscopic interstitial duplications of the X chromosome that included the PLP1 gene were in fact the most frequent cause of PMD, and not just a genetic curiosity [89]. Duplications of the entire PLP1 gene account for about 60-70% of PMD cases [88,[90][91][92]. Duplication of the PLP1 gene probably arises during meiosis in the maternal grandfather in those cases where a new mutation has been found [92,93].…”

Section: The Most Common Cause Of Pmd: Extra Gene Dosage and Overexprmentioning

confidence: 99%

Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis

Garbern

2006

Cell. Mol. Life Sci.

159

147

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Pelizaeus-Merzbacher disease (PMD) and the allelic spastic paraplegia type 2 (SPG2) arise from mutations in the X-linked gene encoding myelin proteolipid protein (PLP). Analysis of mutations affecting PLP, the major protein in central nervous system myelin, has revealed previously unsuspected roles for myelinating glia in maintaining the integrity of the nervous system. The disease spectrum for PMD and SPG2 is extraordinarily broad and can be best understood by accounting not only for the wide range of mutations that can occur but also for the effects of PLP1 mutations on both cell autonomous and non-cell autonomous processes in myelinating cells. Appreciating the wide range of genetic and cellular effects of PLP1 mutations is important for patient and family counseling, understanding disease pathogenesis, and, ultimately, for developing future disease-specific therapies.

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Section: The Most Common Cause Of Pmd: Extra Gene Dosage and Overexprmentioning

confidence: 99%

Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis

Garbern

2006

Cell. Mol. Life Sci.

159

147

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“…Duplications are most frequently encountered, representing 60 to 70% of cases, [42][43][44][45] as depicted in Figure 1. Duplications are most frequently encountered, representing 60 to 70% of cases, [42][43][44][45] as depicted in Figure 1.…”

Section: Duplications Predominate In Patients With Pelizaeus-merzbachmentioning

confidence: 99%

Pelizaeus-Merzbacher Disease and Spastic Paraplegia Type 2

Hudson

2003

J Child Neurol

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Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2 are two sides of the same coin. Both arise from mutations in the gene encoding myelin proteolipid protein. The disease spectrum for Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of Pelizaeus-Merzbacher disease featuring hypotonia, respiratory distress, stridor, nystagmus, and profound myelin loss. The diverse disease spectrum is mirrored by the underlying pathogenesis, in which a blockade at any stage of myelin proteolipid protein synthesis and assembly into myelin spawns a unique phenotype. The continuing definition of pathogenetic mechanisms operative in Pelizaeus-Merzbacher disease and spastic paraplegia type 2, together with advances in neural cell transplant therapy, augurs well for future treatment of the severe forms of Pelizaeus-Merzbacher disease.

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“…The duplication of PLP1 is the most frequent cause of PMD, accounting for 50-70% of PMD cases. In addition, point mutations are identified from 10-25% of PMD patients [6][7][8].…”

Section: Introductionmentioning

confidence: 99%