期刊
NEUROMUSCULAR DISORDERS
卷 25, 期 1, 页码 81-84出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2014.09.008
关键词
Mitochondria; Multisystemic disease; tRNA(Asp)
资金
- German Ministry of Education and Research
- Wellcome Trust Centre for Mitochondrial Research [096919Z/11/Z]
- Medical Research Council (UK) Centre for Translational Muscle Disease research [G0601943]
- Lily Foundation
- UK NHS Highly Specialised Rare Mitochondrial Disorders of Adults and Children Service
- Medical Research Council [G0601943] Funding Source: researchfish
- MRC [G0601943] Funding Source: UKRI
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. (C) 2014 The Authors. Published by Elsevier B.V.
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