title: The m.12316G>A mutation in the mitochondrial tRNA Leu(CUN) gene is associated with mitochondrial myopathy and respiratory impairment.
abstract: Mitochondrial disorders are often associated with mutations in mitochondrial 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.
authors.affiliation: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.forename: Roberta
authors.initials: R
authors.lastname: Virgilio
authors.forename: Andreina
authors.initials: A
authors.lastname: Bordoni
authors.forename: Elisa
authors.initials: E
authors.lastname: Fassone
authors.forename: Monica
authors.initials: M
authors.lastname: Sciacco
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ciscato
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Govoni
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
mesh_terms: D000368:Aged; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012343:RNA, Transfer / Q000235:genetics*
chemical_list: D012343:RNA, Transfer; D003576:Electron Transport Complex IV; D007930:Leucine