title: Identification of novel mutations in five patients with mitochondrial encephalomyopathy.
abstract: MELAS, MERRF, LHON and NARP, are well-established mitochondrial syndromes associated with specific point mutations of mitochondrial DNA (mtDNA). However, these recurrent mtDNA mutations account for only a minority of mitochondrial disease cases. To evaluate the impact of novel mtDNA mutations, we performed mtDNA sequence analysis in muscle and other tissues of 240 patients with different mitochondrial neuromuscular syndromes. We identified a total of 33 subjects with novel, private or uncommon mutations. Among these, five novel mutations were found in both paediatric and adult cases. We here report on the clinical description of these patients, as well as the biochemical and molecular genetic characterization of the corresponding mutations. Patients 1 and 2 showed changes in ND genes, patient 3 carried a heteroplasmic deletion in the COI gene, patients 4 and 5 carried heteroplasmic mutations in tRNA(Trp) and tRNA(Phe), respectively. Altogether, these data indicate that mtDNA analysis must become part of the routine screening for mitochondrial disorders.
authors.affiliation: IRCCS Foundation Neurological Institute C. Besta, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Valente
authors.forename: Daniela
authors.initials: D
authors.lastname: Piga
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lamantea
authors.forename: Franco
authors.initials: F
authors.lastname: Carrara
authors.forename: Graziella
authors.initials: G
authors.lastname: Uziel
authors.forename: Paola
authors.initials: P
authors.lastname: Cudia
authors.forename: Anna
authors.initials: A
authors.lastname: Zani
authors.forename: Laura
authors.initials: L
authors.lastname: Farina
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
authors.forename: Antonella
authors.initials: A
authors.lastname: Spinazzola
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Valeria
authors.initials: V
authors.lastname: Tiranti
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D002648:Child; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008931:Mitochondria, Muscle / Q000235:genetics / Q000473:pathology; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D004247:DNA; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV