A family with paroxysmal nonkinesigenic dyskinesias (PNKD): evidence of mitochondrial dysfunction.
Eur J Paediatr Neurol
; 19(1): 64-8, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-25453601
ABSTRACT
INTRODUCTION:
Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare movement disorder characterized by sudden attacks of involuntary movements. Familial PNKD is an autosomal 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 localization 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. A significant reduction of oxygen consumption and altered calcium homeostasis were found in mutant fibroblasts compared to controls, while no difference was detected in mitochondrial network.CONCLUSIONS:
The data on reduced oxygen consumption and altered calcium homeostasis obtained on mutant fibroblasts are the first evidences, in physiological conditions, of a mitochondrial dysfunction in PNKD.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Corea
/
Enfermedades Mitocondriales
Tipo de estudio:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Paediatr Neurol
Asunto de la revista:
NEUROLOGIA
/
PEDIATRIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Italia