Novel heteroplasmic mutation in the anticodon stem of mitochondrial tRNALys associated with dystonia and stroke-like episodes

作者：Gal A; Pentelenyi K; Remenyi V; Pal Z; Csanyi B; Tomory G; Rasko I; Molnar M J^*

来源：Acta Neurologica Scandinavica, 2010, 122(4): 252-256.

DOI：10.1111/j.1600-0404.2009.01297.x

• dystonia
• stroke-like episode
• lactic acidosis
• anticodon stem mutation
• A8332G
• tRNALys

Objectives -
We report a novel heteroplasmic mitochondrial tRNALys mutation associated with dystonia, stroke-like episodes, sensorineural hearing loss and epilepsy in a Hungarian family.
Material and 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 tRNALys 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.
Conclusion -
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.

• 出版日期2010-10