Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelinating disorder resulting from mutation of the proteolipid protein gene (PLP1). Clinical features of PMD include progressive psychomotor developmental delay, nystagmus, spastic quadriplegia, dystonia, and cerebellar ataxia. PMD is clinically classified into three subtypes according to the severity of the disease: connatal, transitional, and classic forms. Patients with PMD have been identified with duplication, point mutations, and deletion of PLP1. In addition, spastic paraplegia 2 (SPG2) is allelic to PMD and typically caused by missense mutations in the second extracellular domain of PLP1 or in the PLP1-specific region that is spliced out during formation of the DM20 isoform. The authors describe a Korean boy diagnosed with SPG2 caused by a mutation that results in a Pro215Leu substitution in the second extracellular domain. Analysis of phenotypes resulting from mutations affecting PLP1 has been valuable in identifying functional domains of this still incompletely understood major myelin protein. Null mutations and mutations affecting the PLP1-specific domain cause peripheral neuropathy. The PLP1-specific domain also is important in the long-term maintenance of axonal integrity. This patient's phenotype was relatively mild, in contrast with other mutations at position 215 of PLP1 that cause severe PMD. One of these severe mutations is also a missense mutation substituting an aliphatic residue, alanine, for proline. The distinct severity difference between the Pro215Leu and Pro215Ala substitutions suggests that this region of the protein is very sensitive to subtle structural changes and likely plays a critical role in PLP1 function.
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PMID:A case of complicated spastic paraplegia 2 due to a point mutation in the proteolipid protein 1 gene. 1545 Jul 75

Next-generation sequencing was performed for 2 families with an undiagnosed neurologic disease. Analysis revealed X-linked mutations in the proteolipid protein 1 (PLP1) gene, which is associated with X-linked Pelizaeus-Merzbacher disease and Spastic Paraplegia type 2. In family A, the novel PLP1 missense mutation c.617T>A (p.M206K) was hemizygous in the 2 affected male children and heterozygous in the mother. In family B, the novel de novoPLP1 frameshift mutation c.359_369del (p.G120fs) was hemizygous in the affected male child. Although PLP1 mutations have been reported to cause an increasingly wide range of phenotypes inclusive of the dystonia, spastic paraparesis, motor neuronopathy, and leukodystrophy observed in our patients, atypical features included the cerebrospinal fluid deficiency of neurotransmitter and pterin metabolites and the delayed appearance of myelin abnormalities on neuroimaging studies. Next-generation sequencing studies provided a diagnosis for these families with complex leukodystrophy disease phenotypes, which expanded the spectrum of PLP1-associated leukodystrophy clinical phenotypes.
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PMID:Novel PLP1 Mutations Identified With Next-Generation Sequencing Expand the Spectrum of PLP1-Associated Leukodystrophy Clinical Phenotypes. 3004 45