par Lee, Hsien-Yang;Xu, Yi 
;Huang, Yongxiang ;Ahn, Andrew H;Auburger, Georg W J;Pandolfo, Massimo ;Kwiecinski, H;Grimes, David A;Lang, Anthony E;Nielsen, Jorgen E;Averyanov, Yuri;Servidei, Serenella;Friedman, Andrzej;Van Bogaert, Patrick ;Abramowicz, Marc ;Bruno, Marco;Sorensen, Beatrice F;Tang, Ling;Fu, Ying-Hui;Ptácek, Louis J
Référence Human molecular genetics, 13, 24, page (3161-3170)
Publication Publié, 2004-12
;Huang, Yongxiang ;Ahn, Andrew H;Auburger, Georg W J;Pandolfo, Massimo ;Kwiecinski, H;Grimes, David A;Lang, Anthony E;Nielsen, Jorgen E;Averyanov, Yuri;Servidei, Serenella;Friedman, Andrzej;Van Bogaert, Patrick ;Abramowicz, Marc ;Bruno, Marco;Sorensen, Beatrice F;Tang, Ling;Fu, Ying-Hui;Ptácek, Louis JRéférence Human molecular genetics, 13, 24, page (3161-3170)
Publication Publié, 2004-12
Article révisé par les pairs
| Résumé : | 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-1 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. |
