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