A novel m.7539C > T point mutation in the mt-tRNA(Asp) gene associated with multisystemic mitochondrial disease

作者：Lehmann Diana; Schubert Kathrin; Joshi Pushpa R; Baty Karen; Blakely Emma L; Zierz Stephan; Taylor Robert W; Deschauer Marcus^*

来源：Neuromuscular Disorders, 2015, 25(1): 81-84.

DOI：10.1016/j.nmd.2014.09.008

• Mitochondria
• Multisystemic disease
• tRNA(Asp)

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.

• 出版日期2015-1