Novel heteroplasmic mutation in the anticodon stem of mitochondrial tRNA(Lys) associated with dystonia and stroke-like episodes.
OBJECTIVE
We report a novel heteroplasmic mitochondrial tRNA(Lys) mutation associated with dystonia, stroke-like episodes, sensorineural hearing loss and epilepsy in a Hungarian family.


METHODS
A 16-year-old boy, his brother and mother were investigated. Thorough clinical investigation as well as electrophysiological, neuroradiological and myopathological examinations were performed. Molecular studies included the analysis of the DYT1, DDP1/TIMM8A (deafness-dystonia peptid-1) genes and mitochondrial DNA (mtDNA).


RESULTS
The mtDNA analysis of the proband revealed a heteroplasmic A8332G substitution in the anticodon stem of the tRNA(Lys) gene. The mutation segregated in all affected family members. Besides this mutation 16 further mtDNA polymorphisms were detected. Complex I activity of the patient's fibroblast cultures showed decreased activity confirming mitochondrial dysfunction.


CONCLUSIONS
The novel A8332G heteroplasmic mutation is most likely a new cause of dystonia and stroke-like episodes due to mitochondrial encephalopathy. The synergistic effect of the G8697A, A11812G and T10463C single nucleotide polymorphisms may modify the phenotype.
Gal
A
A
Clinical and Research Centre of Molecular Neurology, Semmelweis University, Budapest, Hungary.
Pentelenyi
K
K
Remenyi
V
V
Pal
Z
Z
Csanyi
B
B
Tomory
G
G
Rasko
I
I
Molnar
M J
MJ
D000293:Adolescent; D000926:Anticodon / Q000235:genetics*; D004421:Dystonia / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D006814:Hungary; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D012343:RNA, Transfer / Q000235:genetics*; D020521:Stroke / Q000235:genetics*
D000926:Anticodon; D012343:RNA, Transfer