Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

Johann Böhm; Valérie Biancalana; Elizabeth T Dechene; Marc Bitoun; Christophe Pierson; Elise Schaefer; Hatice Karasoy; Melissa A Dempsey; Fabrice Klein; Nicolas Dondaine; Christine Kretz; Nicolas Haumesser; Claire Poirson; Anne Toussaint; Rebecca S Greenleaf; Melissa A Barger; Lane J Mahoney; Peter B Kang; Edmar Zanoteli; John Vissing; Nanna Witting; Andoni Echaniz-Laguna; Carina Wallgren-Pettersson; James J. Dowling; Luciano Merlini; Anders Oldfors; Lilian Bomme Ousager; Judith Melki; Amanda Krause; Christina Jern; Acary S B Oliveira; Florence Petit; Aurélia Jacquette; Annabelle Chaussenot; David Mowat; Bruno Leheup; Michele Michel; Juan José Poza Aldea; Fabrice Michel; Alain Furby; Jose E Barcena Llona; Rudy C van Coster; Enrico Bertini; Jon Andoni Urtizberea; Valérie Drouin-Garraud; Christophe Béroud; Bernard Prudhon; Melanie Bedford; Katherine Mathews; Lori a H Erby; Stephen A Smith; Jennifer Roggenbuck; Carol A Crowe; Allison Brennan Spitale; Sheila C Johal; Anthony A Amato; Laurie A Demmer; Jessica Jonas; Basil T Darras; Thomas D Bird; Mercy Laurino; Selman I Welt; Cynthia Trotter; Pascale Guicheney; Soma Das; Jean-Louis Mandel; Alan H Beggs; Jocelyn Laporte; Elizabeth T. Dechene; Melissa A. Dempsey; Rebecca S. Greenleaf; Melissa A. Barger; Lane J. Mahoney; Peter B. Kang; Acary S. B. Oliveira; Jose E. Barcena Llona; Lori A. H. Erby; Stephen A. Smith; Carol A. Crowe; Sheila C. Johal; Anthony A. Amato; Laurie A. Demmer; Basil T. Darras; Thomas D. Bird; Selman I. Welt; Alan H. Beggs

doi:10.1002/humu.22067

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Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

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Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

Johann Böhm, Valérie Biancalana, Elizabeth T Dechene, Marc Bitoun, Christophe Pierson, Elise Schaefer, Hatice Karasoy, Melissa A Dempsey, Fabrice Klein, Nicolas Dondaine, …

Human Mutation, Vol.33(6), pp.949 - 959

06/2012

DOI: https://doi.org/10.1002/humu.22067

PMCID: PMC3374402

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.

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Title: Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy
Creators - without role: Johann Böhm - Centre National de la Recherche Scientifique
Valérie Biancalana - Inserm
Elizabeth T Dechene - Harvard University
Marc Bitoun - Inserm
Christophe Pierson
Elise Schaefer - Hôpital Civil, Strasbourg
Hatice Karasoy - Ege University
Melissa A Dempsey - University of Chicago
Fabrice Klein - Inserm
Nicolas Dondaine - Hôpital Civil, Strasbourg
Christine Kretz - Inserm
Nicolas Haumesser - Inserm
Claire Poirson - Inserm
Anne Toussaint - Inserm
Rebecca S Greenleaf - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Melissa A Barger - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Lane J Mahoney - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Peter B Kang - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Edmar Zanoteli - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
John Vissing - University of Copenhagen
Nanna Witting - University of Copenhagen
Andoni Echaniz-Laguna - Hôpital Civil, Strasbourg
Carina Wallgren-Pettersson - Folkhälsans Forskningscentrum
James J. Dowling - University of Michigan–Ann Arbor
Luciano Merlini - Istituto Ortopedico Rizzoli
Anders Oldfors - Sahlgrenska University Hospital
Lilian Bomme Ousager
Judith Melki - Inserm
Amanda Krause - National Health Laboratory Service
Christina Jern - University of Gothenburg
Acary S B Oliveira - Universidade Federal de São Paulo
Florence Petit - Centre Hospitalier Universitaire de Lille
Aurélia Jacquette - Pitié-Salpêtrière Hospital
Annabelle Chaussenot - Centre Hospitalier Universitaire de Nice
David Mowat - Sydney Children's Hospital
Bruno Leheup - Université de Lorraine
Michele Michel
Juan José Poza Aldea
Fabrice Michel - Centre Hospitalier Universitaire de Besançon
Alain Furby - Hôpital Nord
Jose E Barcena Llona
Rudy C van Coster - Ghent University Hospital
Enrico Bertini - Bambino Gesù Children's Hospital
Jon Andoni Urtizberea - Hôpital Marin de Hendaye
Valérie Drouin-Garraud - Service de génétique [Rouen]
Christophe Béroud - Université de Montpellier, Physiologie et Médecine Expérimentale du coeur et des muscles - PhyMedExp
Bernard Prudhon - Inserm
Melanie Bedford - North York General Hospital
Katherine Mathews - University of Iowa
Lori a H Erby - Johns Hopkins University
Stephen A Smith - Hennepin County Medical Center
Jennifer Roggenbuck - Children's Minnesota
Carol A Crowe - MetroHealth Medical Center
Allison Brennan Spitale
Sheila C Johal - MetroHealth Medical Center
Anthony A Amato - Harvard University
Laurie A Demmer - Tufts Medical Center
Jessica Jonas - Tufts Medical Center
Basil T Darras - Boston Children's Hospital
Thomas D Bird - University of Washington Medical Center
Mercy Laurino - University of Washington
Selman I Welt - Texas Tech University Health Sciences Center
Cynthia Trotter - Texas Tech University Health Sciences Center
Pascale Guicheney - Inserm
Soma Das - University of Chicago
Jean-Louis Mandel - Institut de génétique et de biologie moléculaire et cellulaire
Alan H Beggs - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Jocelyn Laporte - Inserm
Elizabeth T. Dechene - Harvard University
Melissa A. Dempsey - University of Chicago
Rebecca S. Greenleaf - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Melissa A. Barger - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Lane J. Mahoney - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Peter B. Kang - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Acary S. B. Oliveira - Universidade Federal de São Paulo
Jose E. Barcena Llona
Lori A. H. Erby - Johns Hopkins University
Stephen A. Smith - Hennepin County Medical Center
Carol A. Crowe - MetroHealth Medical Center
Sheila C. Johal - MetroHealth Medical Center
Anthony A. Amato - Harvard University
Laurie A. Demmer - Tufts Medical Center
Basil T. Darras - Boston Children's Hospital
Thomas D. Bird - University of Washington Medical Center
Selman I. Welt - Texas Tech University Health Sciences Center
Alan H. Beggs - Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Publication Details: Human Mutation, Vol.33(6), pp.949 - 959
Identifiers: 9933748009311
Academic Unit: Physiologie et Médecine Expérimentale du coeur et des muscles - PhyMedExp
Language: English
Resource Type: Journal article
Local Fields: hal-01681807