title: A novel dynamin-2 gene mutation associated with a late-onset centronuclear myopathy with necklace fibres.
abstract: Nuclear centralisation and internalisation, sarcoplasmic radiating strands and type 1 muscle fibre predominance and hypotrophy characterise dynamin-2 (DNM2) associated centronuclear myopathy, whereas necklace fibres are typically seen in late onset myotubularin-1 (MTM1)-related myopathy. We report a woman with unilateral symptoms probably related to brachial plexus neuritis. Electromyography revealed localised neuropathic and generalised myopathic abnormalities. The typical features of DNM2 centronuclear myopathy with additional necklace fibres were found in the muscle biopsy. Sequencing of the DNM2 and MTM1 genes revealed a novel heterozygous missense mutation in exon 18 of the DNM2, leading to replacement of highly conserved proline at position 647 by arginine. The muscle symptoms have not progressed during the 3-year follow-up. However, the patient has developed bilateral subtle lens opacities. Our findings support the concept that necklace fibres may occasionally be found in DNM2-related myopathy, possibly indicating a common pathogenic mechanism in DNM2 and MTM1 associated centronuclear myopathy.
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Clinical Pathology and Cytology, Uppsala University Hospital, Uppsala, Sweden. Electronic address: olivera.casar-borota@igp.uu.se.
authors: Olivera
authors: O
authors: Casar-Borota
authors: Institution of Pharmacology and Clinical Neuroscience, Section of Neurology, Umeå University, Umeå, Sweden.
authors: Johan
authors: J
authors: Jacobsson
authors: Institution of Pharmacology and Clinical Neuroscience, Section of Neurology, Umeå University, Umeå, Sweden.
authors: Rolf
authors: R
authors: Libelius
authors: Department of Pathology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Carola Hedberg
authors: CH
authors: Oldfors
authors: Myology Institute, Neuromuscular Morphology Unit, Groupe Hospitalier Universitaire La Pitié-Salpétriére, Sorbonne Universités UPMC Univ, Paris 06, Paris, France.
authors: Edoardo
authors: E
authors: Malfatti
authors: Myology Institute, Neuromuscular Morphology Unit, Groupe Hospitalier Universitaire La Pitié-Salpétriére, Sorbonne Universités UPMC Univ, Paris 06, Paris, France.
authors: Norma Beatriz
authors: NB
authors: Romero
authors: Department of Pathology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Anders
authors: A
authors: Oldfors
mesh_terms: D000328:Adult; D017668:Age of Onset; D034285:Dynamin II; D034281:Dynamins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018482:Muscle, Skeletal / Q000473:pathology; D020125:Mutation, Missense; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins
keywords: Centronuclear myopathy; Dynamin 2; Necklace fibre