title: The coexistence of dynamin 2 mutation and multiple mitochondrial DNA (mtDNA) deletions in the background of severe cardiomyopathy and centronuclear myopathy.
abstract: Dynamin2 (DNM2) gene mutations may result in Charcot-Marie-Tooth disease and centronuclear myopathy. Here, we present a patient suffering from cardiomyopathy and centronuclear myopathy with repetitive discharges and mild axonal neuropathy due to DNM2 mutation. Detailed cardiological and neurological examinations, electrophysiological tests, muscle biopsy, and molecular genetic analysis were performed. The patient developed left bundle branch block at age 40 and was fitted with a pacemaker at the age of 43. The patient has severe heart failure, ptosis, strabism, facial and proximal muscle weakness. Electrophysiological investigations found myopathy, complex repetitive discharges, and axonal neuropathy. Skeletal muscle biopsy detected centronuclear myopathy and cytochrome C oxidase (COX) negative fibers. Genetic analysis detected a pathogenic c.1105C>T (p.R369W) DNM2 gene mutation and heteroplasmic multiple mitochondrial DNA (mtDNA) deletion. Our data broadens the phenotypic spectrum of DNM2 mutations. The presence of the multiple mtDNA deletions may provide new aspects to understanding the pathogenesis of multisystemic symptoms in patients with DNM2 mutations.
authors.forename: Aniko
authors.initials: A
authors.lastname: Gal
authors.forename: Gabriella
authors.initials: G
authors.lastname: Inczedy-Farkas
authors.forename: Endre
authors.initials: E
authors.lastname: Pal
authors.forename: Viktoria
authors.initials: V
authors.lastname: Remenyi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bereznai
authors.forename: Laszlo
authors.initials: L
authors.lastname: Geller
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szelid
authors.forename: Bela
authors.initials: B
authors.lastname: Merkely
authors.forename: Maria Judit
authors.initials: MJ
authors.lastname: Molnar
mesh_terms: D015139:Blotting, Southern; D009202:Cardiomyopathies / Q000235:genetics* / Q000503:physiopathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D034285:Dynamin II; D034281:Dynamins / Q000235:genetics*; D004594:Electrophysiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins