The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway

Hsien-Yang Lee, Ying Xu, Yong Huang, Andrew H. Ahn, Georg W.J. Auburger, Massimo Pandolfo, Hubert Kwieciński, David A. Grimes, Anthony E. Lang, Jorgen E. Nielsen, Yuri Averyanov, Serenella Servidei, Andrzej Friedman, Patrick Van Bogaert, Marc J. Abramowicz, Michiko K. Bruno, Beatrice F. Sorensen, Ling Tang, Ying-Hui Fu, Louis J. Ptáček

Risultato della ricerca: Contributo in rivistaArticolo in rivista

139 Citazioni (Scopus)


Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous hyperkinetic attacks that are precipitated by alcohol, coffee, stress and fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene causing PNKD in 50 individuals from eight families. The mutations cause changes (Ala to Val) in the N-terminal region of two MR-1L isoforms. The MR-1L isoform is specifically expressed in brain and is localized to the cell membrane while the MR-1S isoform is ubiquitously expressed and shows diffuse cytoplasmic and nuclear localization. Bioinformatic analysis reveals that the MR-1 gene is homologous to the hydroxyacylglutathione hydrolase (HAGH) gene. HAGH functions in a pathway to detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and produced as a by-product of oxidative stress. Our results suggest a mechanism whereby alcohol, coffee and stress may act as precipitants of attacks in PNKD. Stress response pathways will be important areas for elucidation of episodic disease genetics where stress is a common precipitant of many common disorders like epilepsy, migraine and cardiac arrhythmias. © Oxford University Press 2004; all rights reserved.
Lingua originaleEnglish
pagine (da-a)3161-3170
Numero di pagine10
RivistaHuman Molecular Genetics
Stato di pubblicazionePubblicato - 2004


  • Animals
  • Central Nervous System
  • Chorea
  • Chromosome Mapping
  • Female
  • Genetics
  • Genetics (clinical)
  • Humans
  • In Situ Hybridization
  • Male
  • Mice
  • Molecular Biology
  • Muscle Proteins
  • Mutation
  • Pedigree
  • Protein Isoforms
  • Sequence Analysis, DNA
  • Stress, Physiological


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