Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant cerebellar ataxia characterized clinically by myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia with personality change. Histopathologically, DRPLA is characterized by a unique combination of degenerative changes in both the dentatofugal and the pallidofugal systems. Credit for the establishment of DRPLA as an entity is given to Naito and Oyagagi, who first noticed a strong heritability and an age of onset-dependent variability of the clinical features. Most papers on DRPLA research are written in Japanese, and are extensively reviewed here. After the gene was identified in 1994, DRPLA became known as one of the CAG repeat expansion diseases, in which the responsible gene is located on chromosome 12p and its product is called atrophin-1. Classical genetics revealed that DRPLA shows prominent "anticipation" and modern molecular genetics provided a clear explanation for this phenomenon, by demonstrating a strong instability of the expanded CAG repeat length through generations. The impact of gene analysis of DRPLA on the clinical genetics and neurology are discussed. Moreover, possible mechanism(s) underlying the neuronal cell death in DRPLA are discussed in terms of the molecular pathology.
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PMID:Dentatorubral-pallidoluysian atrophy or Naito-Oyanagi disease. 993 95

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder clinically characterized by various combinations of cerebellar ataxia, choreoathetosis, myoclonus, epilepsy, dementia, and psychiatric symptoms. The most striking clinical features of DRPLA are the considerable heterogeneity in clinical presentation, depending on the age of onset, and the prominent genetic anticipation. DRPLA is caused by unstable expansion of CAG repeats coding for polyglutamine stretches located in exon 5 of the DRPLA gene. DRPLA is characterized by prominent anticipation, with paternal transmission resulting in more prominent anticipation than does maternal transmission, which is now understood based on the intergenerational stability of the CAG repeats. DRPLA protein (also called atrophin-1) is localized in the nucleus and functions as a transcription co-regulator. Recent immunohistochemical studies on autopsied tissues of patients with DRPLA have demonstrated that diffuse accumulation of mutant DRPLA protein (atrophin-1) in the neuronal nuclei, rather than the formation of neuronal intranuclear inclusions (NIIs), is the predominant pathologic condition and involves a wide range of central nervous system regions far beyond the systems previously reported to be affected. Thus, age-dependent and CAG repeat-dependent intranuclear accumulation of mutant DRPLA leading to nuclear dysfunctions are suggested to be the essential pathophysiologic mechanisms in DRPLA.
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PMID:Dentatorubral-pallidoluysian atrophy. 2182 19