Introduction:\ud Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare movement disorder\ud characterized by sudden attacks of involuntary movements. Familial PNKD is an auto-\ud somal dominant trait, caused by mutations in the myofibrillogenesis regulator 1 (\ud MR-1\ud )\ud gene on chromosome 2q35. Three different mutations have been described; all of them\ud reside in the N-terminal region common to isoforms L and S, that has been suggested to\ud code for a mitochondrial targeting sequence, necessary for the correct sub-cellular locali-\ud zation of the protein into mitochondria.\ud Methods:\ud We report on four patients of the same family, affected by PNKD. Skin fibroblasts\ud were used to analysed oxygen consumption and to measure mitochondrial matrix calcium\ud response after agonist stimulation. Mitotracker-based visualization was also used to assess\ud fragmentation of the mitochondrial network.\ud Results:\ud the paroxysmal movements were dystonic in two patients and dystonic/choreiform\ud in the other ones; in three cases the symptoms started in one limb and then generalized,\ud while in one case remained focal. Three had a very early onset, within the first two years of\ud life. The frequency of episodes showed a great variability, ranging from 2 times a day to 3\ud times a year, while the duration of the attacks ranged from 2 min to 1,5 h, always with\ud sudden onset and end and complete recover in between. All affected subjects harbored a\ud heterozygous C to T substitution in\ud MR-1\ud , causing an Ala9Val amino acid change in the N-\ud terminal region
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