title: The novel mitochondrial tRNAAsn gene mutation m.5709T>C produces ophthalmoparesis and respiratory impairment.
abstract: Although mutations in mitochondrial tRNAs constitute the most common mtDNA defect, the presence of pathological variants in mitochondrial tRNA(Asn) is extremely rare. We were able to identify a novel mtDNA tRNA(Asn) gene pathogenic mutation associated with a myopathic phenotype and a previously unreported respiratory impairment. Our proband is an adult woman with ophthalmoparesis and respiratory impairment. Her muscle biopsy presented several cytochrome c oxidase-negative (COX-) fibres and signs of mitochondrial proliferation (ragged red fibres). Sequence analysis of the muscle-derived mtDNA revealed an m.5709T>C substitution, affecting mitochondrial tRNA(Asn) gene. Restriction-fragment length polymorphism analysis of the mutation in isolated muscle fibres showed that a threshold of at least 91.9% mutated mtDNA results in the COX deficiency phenotype. The new phenotype further increases the clinical spectrum of mitochondrial diseases caused by mutations in the tRNA(Asn) gene.
authors.affiliation: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.forename: Monica
authors.initials: M
authors.lastname: Sciacco
authors.forename: Andreina
authors.initials: A
authors.lastname: Bordoni
authors.forename: Monika
authors.initials: M
authors.lastname: Raimondi
authors.forename: Michela
authors.initials: M
authors.lastname: Ripolone
authors.forename: Elisa
authors.initials: E
authors.lastname: Fassone
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Fonzo
authors.forename: Mafalda
authors.initials: M
authors.lastname: Rizzuti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ciscato
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cosi
authors.forename: Maura
authors.initials: M
authors.lastname: Servida
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
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: D001483:Base Sequence; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D009154:Mutation; D009886:Ophthalmoplegia / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012348:RNA, Transfer, Asn / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D000077278:RNA, Mitochondrial; D012348:RNA, Transfer, Asn; D012313:RNA; D003576:Electron Transport Complex IV