Identification of variants in the mitochondrial lysine-tRNA (MT-TK) gene in myoclonic epilepsy—pathogenicity evaluation and structural characterization by in silico approach

Identification of variants in the mitochondrial lysine-tRNA (MT-TK) gene in myoclonic epilepsy—pathogenicity evaluation and structural characterization by in silico approach

Abstract

Variations in mitochondrial genes have an established link with myoclonic epilepsy. In
the present study we evaluated the nucleotide sequence of MT-TK gene of 52
individuals from 12 unrelated families and reported three variations in 2 of the 13
epileptic patients. The DNA sequences coding for MT-TK gene were sequenced and
mutations were detected in all participants. The mutations were further analyzed by the
in silico analysis and their structural and pathogenic effects were determined. All the
investigated patients had symptoms of myoclonus, 61.5% were positive for ataxia,
23.07% were suffering from hearing loss, 15.38% were havingmild to severe dementia,
69.23% were males, and 61.53% had cousin marriage in their family history. DNA
extracted from saliva was used for the PCR amplification of a 440 bp DNA fragment
encompassing complete MT-TK gene. The nucleotide sequence analysis revealed three
mutations, m.8306T>C, m.8313G>C, and m.8362T>G that are divergent from
available reports. The identified mutations designate the heteroplasmic condition.
Furthermore, pathogenicity of the identified variants was predicted by in silico tools
viz., PON-mt-tRNA and MitoTIP. Secondary structure of altered MT-TK was
predicted by RNAStructure web server. Studies by MitoTIP and PON-mt-tRNA tools
have provided strong evidences of pathogenic effects of these mutations. Single
nucleotide variations resulted in disruptive secondary structure of mutant MT-TK
models, as predicted by RNAStructure. In vivo confirmation of structural and
pathogenic effects of identifiedmutations in the animalmodels can be prolonged on the
basis of these findings
 

No. of Pages
1-8
Volume
12
Author's Details
Muhammad S. Nadeem, H. Ahmad, K. Mohammed, I. ullah, O. A. S. Baothman, N.ali, F. Anwar, M. A. Zamzami and A. R. Shakoori
Research Field
Human Genetics