A novel m.7539C>T point mutation in the mt-tRNA(Asp) gene associated with multisystemic mitochondrial disease.
|
| Abstract |
Mitochondrial transfer RNA (mt-tRNA) mutations are the commonest sub-type of mitochondrial (mtDNA) mutations associated with human disease. We report a patient with multisytemic disease characterised by myopathy, spinal ataxia, sensorineural hearing loss, cataract and cognitive impairment in whom a novel m.7539C>T mt-tRNA(Asp) transition was identified. Muscle biopsy revealed extensive histopathological findings including cytochrome c oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for the mutation whilst single muscle fibre segregation studies revealed statistically significant higher mutation loads in COX-deficient fibres than in COX-positive fibres. Absence from control databases, hierarchical mt-tRNA mutation segregation within tissues, and occurrence at conserved sequence positions, further confirm this novel mt-tRNA mutation to be pathogenic. To date only three mt-tRNA(Asp) gene mutations have been described with clear evidence of pathogenicity. The novel m.7539C>T mt-tRNA(Asp) gene mutation extends the spectrum of pathogenic mutations in this gene, further supporting the notion that mt-tRNA(Asp) gene mutations are associated with multisystemic disease presentations.
|
|---|---|
| Authors | Diana Lehmann, Kathrin Schubert, Pushpa R Joshi, Karen Baty, Emma L Blakely, Stephan Zierz, Robert W Taylor, Marcus Deschauer |
| Journal | Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 25 Issue 1 Pg. 81-4 (Jan 2015) ISSN: 1873-2364 [Electronic] England |
| PMID | 25447692 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!