Journal article
Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy
Human mutation, Vol.33(6), pp.949-959
06/2012
DOI: 10.1002/humu.22067
PMID: 22396310
Abstract
Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.
Details
- Title: Subtitle
- Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy
- Creators
- Johann Böhm - Institut de Génétique et de Biologie Moléculaire et CellulaireValérie Biancalana - Institut de Génétique et de Biologie Moléculaire et CellulaireElizabeth T DecheneMarc Bitoun - Institut de MyologieChristophe PiersonElise Schaefer - Service de génétique médicaleHatice Karasoy - Department of NeurologyMelissa A DempseyFabrice KleinNicolas DondaineChristine Kretz - Institut de Génétique et de Biologie Moléculaire et CellulaireNicolas HaumesserClaire PoirsonAnne Toussaint - Institut de génétique et biologie moléculaire et cellulaireRebecca S GreenleafMelissa A BargerLane J MahoneyPeter B KangEdmar ZanoteliJohn Vissing - Applied human geneticsNanna WittingAndoni Echaniz-Laguna - Département de NeurologieCarina Wallgren-Pettersson - Department of Medical and Clinical Genetics [Helsinki]James Dowling - Department of PediatricsLuciano Merlini - CNRAnders OldforsLilian Bomme OusagerJudith Melki - Hôpital BicêtreAmanda Krause - Division of human GeneticsChristina Jern - Insitute of Neuroscience and PhysiologyAcary S B OliveiraFlorence Petit - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837Aurélia Jacquette - Institut de MyologieAnnabelle Chaussenot - Institut de Recherche sur le Cancer et le VieillissementDavid MowatBruno Leheup - Service de Génétique Médicale [CHRU Nancy]Michele MichelJuan José Poza AldeaFabrice Michel - VEGATECAlain Furby - Service de NeurologieJose E Barcena LlonaRudy Van Coster - Department of PediatricsEnrico Bertini - Dept. Medical Biochemistry, Biology and PhysicsJon Andoni UrtizbereaValérie Drouin-Garraud - Service de génétique [Rouen]Christophe Béroud - Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiquesBernard Prudhon - Institut de MyologieMelanie BedfordKatherine MathewsLori A H ErbyStephen A SmithJennifer RoggenbuckCarol A Crowe - Department of PediatricsAllison Brennan SpitaleSheila C JohalAnthony A AmatoLaurie A DemmerJessica JonasBasil T DarrasThomas D BirdMercy LaurinoSelman I WeltCynthia TrotterPascale Guicheney - Unité UMR_S956Soma Das - Entomology Research Unit, Department of ZoologyJean-Louis Mandel - Institut de Génétique et de Biologie Moléculaire et CellulaireJocelyn Laporte - Institut de Génétique et de Biologie Moléculaire et CellulaireAlan H Beggs - Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.33(6), pp.949-959
- Publisher
- Wiley
- DOI
- 10.1002/humu.22067
- PMID
- 22396310
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Language
- English
- Date published
- 06/2012
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984013110002771
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