title: Pure myopathy with enlarged mitochondria associated to a new mutation inMTND2gene.
abstract: To date, only few mutations in the mitochondrial DNA (mtDNA)-encoded ND2 subunit of Complex I have been reported, usually presenting a severe phenotype characterized by early onset encephalomyopathy and early death. In this report, we describe a new mutation in theMTND2gene in a 21-year-old man with a mild myopathic phenotype characterized by exercise intolerance and increased plasma lactate at rest. Electromyography and brain NMR were normal, and no cardiac involvement was present. Muscle biopsy showed a massive presence of ragged red - COX-positive fibres, with enlarged mitochondria containing osmiophilic inclusions. Biochemical assays revealed a severe isolated complex I deficiency. We identified a novel, heteroplasmic mutation m.4831G > A in theMTND2gene, causing the p.Gly121Asp substitution in the ND2 protein. The mutation was present in the 95% of mitochondrial genomes from patient's muscle tissue, at a lower level in cells from the urinary tract and at a lowest level in lymphocytes from patient's blood; the base substitution was absent in fibroblasts and in the tissues from proband's healthy mother and brother. The specific skeletal muscle tissue involvement can explain the childhood-onset and the relatively benign, exclusively myopathic course of the disease.
authors.affiliation: Unit of Molecular Neurogenetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Zanolini
authors.affiliation: Clinic for Child Neurology and Psychiatry, Department of Neurology, Medical Faculty University of Belgrade, Belgrade 11000, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Potic
authors.affiliation: Unit of Molecular Neurogenetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Carrara
authors.affiliation: Unit of Molecular Neurogenetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lamantea
authors.affiliation: Unit of Molecular Neurogenetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy; Division of Neuromuscular and Neurodegenerative Disorders, Ospedale Pediatrico Bambin Gesu, Rome, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Diodato
authors.affiliation: IV Division of Neurology, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Blasevich
authors.affiliation: Unit of Molecular Neurogenetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marchet
authors.affiliation: IV Division of Neurology, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
authors.affiliation: Dept of Surgical and Morphological Sciences, University of Insubria, Varese, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallotti
authors.affiliation: IV Division of Neurology, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.affiliation: Unit of Molecular Neurogenetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy; Mitochondrial Biology Unit, Medical Research Council, Cambridge CB2 0XY, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.affiliation: Unit of Molecular Neurogenetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20126 Milan, Italy.
authors.forename: Costanza
authors.initials: C
authors.lastname: Lamperti
keywords: Complex I deficiency; Exercise intolerance; ND2