Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0004134 (
ataxia
)
15,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Polymorphism of highly polymorphic triplet repeats CTG of the 3'-untranslated region of the
myotonin protein kinase
gene and CAG of the genes associated with dentatorobral-pallidoluysian atrophy (DRPLA, or Hew River syndrome) and spinocerebellar
ataxia
type 1 (SCA1) was analyzed in several ethnic populations of Russia. A difference in allele spectra of the three genes was demonstrated for populations differing in ethnic origin.
...
PMID:[Analysis of the allele polymorphism of (CTG)n and (GAG)n triplet repeats in DM, DRPLA, and SCA1 genes in various populations of Russia]. 1250 Jun 81
Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion mutation located in the 3' untranslated portion of the dystrophica
myotonin protein kinase
gene. The identification and characterization of RNA-binding proteins that interact with expanded CUG repeats and the discovery that a similar transcribed but untranslated CCTG expansion in an intron causes myotonic dystrophy type 2 (DM2) have uncovered a new type of mechanism in which microsatellite expansion mutations cause disease through an RNA gain-of-function mechanism. This review discusses RNA pathogenesis in DM1 and DM2 and evidence that similar mechanisms may play a role in a growing number of dominant noncoding expansion disorders, including fragile X tremor
ataxia
syndrome (FXTAS), spinocerebellar
ataxia
type 8 (SCA8), SCA10, SCA12, and Huntington's disease-like 2 (HDL2).
...
PMID:RNA-mediated neuromuscular disorders. 1677 86
Dozens of incurable neurological disorders result from expansion of short repeat sequences in both coding and non-coding regions of the transcriptome. Short repeat expansions underlie microsatellite repeat expansion (MRE) disorders including myotonic dystrophy (DM1, CUG
50-3,500
in
DMPK
; DM2, CCTG
75-11,000
in ZNF9), fragile X tremor
ataxia
syndrome (FXTAS, CGG
50-200
in FMR1), spinal bulbar muscular atrophy (SBMA, CAG
40-55
in AR), Huntington's disease (HD, CAG
36-121
in HTT), C9ORF72- amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD and C9-ALS/FTD, GGGGCC in C9ORF72), and many others, like ataxias. Recent research has highlighted several mechanisms that may contribute to pathology in this heterogeneous class of neurological MRE disorders - bidirectional transcription, intranuclear RNA foci, and repeat associated non-AUG (RAN) translation - which are the subject of this review. Additionally, many MRE disorders share similar underlying molecular pathologies that have been recently targeted in experimental and preclinical contexts. We discuss the therapeutic potential of versatile therapeutic strategies that may selectively target disrupted RNA-based processes and may be readily adaptable for the treatment of multiple MRE disorders. Collectively, the strategies under consideration for treatment of multiple MRE disorders include reducing levels of toxic RNA, preventing RNA foci formation, and eliminating the downstream cellular toxicity associated with peptide repeats produced by RAN translation. While treatments are still lacking for the majority of MRE disorders, several promising therapeutic strategies have emerged and will be evaluated within this review.
...
PMID:Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies. 3317 4
