The m.12316G > A mutation in the mitochondrial tRNA(Leu(CUN)) gene is associated with mitochondrial myopathy and respiratory impairment

作者：Ronchi Dario; Virgilio Roberta; Bordoni Andreina; Fassone Elisa; Sciacco Monica; Ciscato Patrizia; Moggio Maurizio; Govoni Alessandra; Corti Stefania; Bresolin Nereo; Comi Giacomo P^*

来源：Journal of the Neurological Sciences, 2010, 292(1-2): 107-110.

DOI：10.1016/j.jns.2010.01.026

• mtDNA
• tRNA(Leu(CUN))
• Late-onset myopathy

Mitochondrial disorders are often associated with mutations in mitochondria! tRNA. Independent observation of the same molecular defect in unrelated subjects is a generally required proof of pathogenicity. A sporadic case of chronic external ophthalmoplegia (cPEO) with ragged red fibres (RRFs) has been previously related to an m.12316G>A substitution in tRNA(Leu(CUN)).
Sequencing muscle-derived mtDNA, we found the m.12316G>A substitution in an adult woman with mitochondrial myopathy and respiratory impairment. Her muscle biopsy presented several cytochrome c oxidase-negative (COX) fibres, and RRFs as signs of mitochondrial proliferation. Restriction-fragment length polymorphism (RFLP) analysis of the mutation in isolated muscle fibres showed a threshold of at least 60% of mutated mtDNA to determine a COX deficiency phenotype. This second report of the m.12316G>A mutation in a sporadic patient consolidates its pathogenic nature and provides further elements for genetic counselling.

• 出版日期2010-5-15