Pelizaeus-Merzbacher disease (PMD) is an X-linked leukodystrophy caused by mutations in Proteolipid Protein 1 (PLP1), encoding a major myelin protein, resulting in profound developmental delay and early lethality.
We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD; MIM: 312080).
Together, our results provide evidence that AAV-mediated gene suppression therapy can serve as a potential cure for PMD resulting from PLP1 duplication and possibly for other genomic disorders.
In this chapter, I discuss the historical aspects and current understanding of the mechanisms underlying how different PLP1 mutations disrupt the normal process of myelination and result in PMD and other disorders.
Additionally, a single intracerebroventricular injection of MO-PLP into the brains of neonatal mice, carrying a deletion of an intronic splicing enhancer identified in a PMD patient that reduces the Plp1 spliced form, corrected alternative splicing at both RNA and protein levels in the CNS.
We detected a novel pathogenic PLP1 missense mutation c.251C > A (p.Ala84Asp) allowing us to make a diagnosis of Pelizaeus-Merzbacher Disease for this family.
Pelizaeus-Merzbacher disease (PMD; MIM 312080), an inherited defect of central nervous system myelin formation, affects individuals in many ways, including their hearing and language abilities.
Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder caused by mutations in the PLP1 gene, which encodes the proteolipid protein of myelinating oligodendroglia.
The Plp1 overexpressing mouse model (PLP-tg<sup>66/66</sup> ) develops a phenotype very similar to human PMD, with early and severe motor dysfunction and a dramatic decrease in lifespan.
Alterations in the myelin proteolipid protein gene ( PLP1) may result in rare X-linked disorders in humans such as Pelizaeus-Merzbacher disease and spastic paraplegia type 2.
Long-range polymerase chain reaction (PCR) is a traditional approach to obtain CNV breakpoint junction, but this method is inefficient when challenged by structural complexity such as often found at the PLP1 locus in association with Pelizaeus-Merzbacher disease (PMD).
Collectively, these data provide insights into the pathogeneses of a variety of PLP1 mutations and suggest that disparate etiologies of PMD could require specific treatment approaches for subsets of individuals.
Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder caused by mutation in the proteolipid protein-1 (PLP1) gene, which encodes the proteolipid protein of myelinating oligodendroglia.
The proteolipid protein 1 gene (PLP1) is located on chromosome Xq22.2 and is related to X-linked recessive leukoencephalopathy (Pelizaeus-Merzbacher disease: PMD).
To the best of our knowledge this is the first time that this novel mutation H133P of PLP1 gene is identified and clinically associated with optic nerve enlargement in PMD patients.
This review discusses how PLP1 mutant proteins change protein homeostasis in the ER of oligodendrocytes, especially focusing on the reaction of ER chaperones against the accumulation of PLP1 mutant proteins that cause PMD.
Pelizaeus-Merzbacher disease and spastic paraplegia type 2 are allelic X-linked disorders associated with defective myelination of the central nervous system and mutations in PLP1.
Pelizaeus-Merzbacher disease (PMD) is X-linked hypomyelinating leukodystrophy caused by mutations of the PLP1 gene, which codes the proteolipid protein 1.
The hypomyelinating leukodystrophies (HMLs) encompass the X-linked Pelizaeus-Merzbacher disease (PMD) caused by PLP1 mutations and known as the classical form of HML as well as Pelizaeus-Merzbacher-like disease (PMLD) (Online Mendelian Inheritance in Man [OMIM] 608804 and OMIM 260600) due to GJC2 mutations.
Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating leukodystrophy resulting from proteolipid protein 1 gene (PLP1) mutations leading to oligodendrocyte loss.
While her phenotypic features such as cognitive impairment and motor delay show overlap with Pelizaeus-Merzbacher disease (PMD) caused by PLP1 mutations at Xq22.2, this gene is not included in our patient's microdeletion and is not dysregulated by a position effect.