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ACTA MYOLOGICA (Myopathies, Cardiomyopathies and Neuromyopathies) ISSN 1128-2460 AC T Established in 1982 as Cardiomyology A M YOLOGICA ACTA MYOLOGICA (Myopathies, Cardiomyopathies and Neuromyopathies) Vol. XXXIII - May 2014 Official Journal of CB PISA D Mediterranean Society of Myology and Associazione Italiana di Miologia Founders: Giovanni Nigro and Lucia Ines Comi VOL. XXXIII N. 1 - 2014 XXXIII N. VOL. Four-monthly EDITOR-IN-CHIEF Giovanni Nigro ASSISTANT EDITOR managing EDITOR .L. 353/2003 conv. in L. 27/02/2004 n° 46 art. 1, comma 1, comma 1, 27/02/2004 1, in L. n° 46 art. 353/2003 .L. conv. D Vincenzo Nigro Luisa Politano CO-EDITORS Valerie Askanas Giuseppe Novelli Lefkos Middleton Reinhardt Rüdel HISTORical STUDIES EDITOR Georges Serratrice ALIANE SPA - Spedizione in Abbonamento Postale - Postale Abbonamento - Spedizione in ALIANE SPA T E I T POS Official Journal of Mediterranean Society of Myology and Associazione Italiana di Miologia Founders: Giovanni Nigro and Lucia Ines Comi Four-monthly EDITORIAL BOARD Ekram Abdel-Salam, Cairo Clemens Müller, Würzburg Corrado Angelini, Padova Francesco Muntoni, Londra Enrico Bertini, Roma Carmen Navarro, Vigo Serge Braun, Paris Gerardo Nigro, Napoli Kate Bushby, Newcastle upon Tyne Anders Oldfors, Göteborg Kevin P. Campbell, Iowa City Eijiro Ozawa, Tokyo Marinos Dalakas, Athens Heinz Reichmann, Dresden Feza Deymeer, Instanbul Serenella Servidei, Roma Salvatore Di Mauro, New York Piraye Serdaroglu, Instanbul Denis Duboc, Paris Yeuda Shapira, Jerusalem Victor Dubowitz, London Osman I. Sinanovic, Tuzla King W. Engel, Los Angeles Michael Sinnreich, Montreal Michel Fardeau, Paris Andoni J. Urtizberea, Hendaye Irena Hausmanowa-Petrusewicz, Warszawa Gert-Jan van Ommen, Leiden Fayçal Hentati, Tunis Lord John Walton of Detchant, Oxford Byron A. Kakulas, Perth Steve Wilton, Perth Frank Lehmann-Horn, Ulm Klaus Zerres, Aachen Carlo Minetti, Genova Janez Zidar, Ljubliana EDITOR-IN-CHIEF CO-EDITORS Giovanni Nigro, Napoli Valerie Askanas, Los Angeles Lefkos Middleton, Nicosia ASSISTANT EDITOR Giuseppe Novelli, Roma Vincenzo Nigro, Napoli Reinhardt Rüdel, Ulm MANAGING EDITOR HISTORICAL STUDIES EDITOR Luisa Politano, Napoli Georges Serratrice, Marseille BOARD OF THE MEDITERRANEAN SOCIETY OF MYOLOGY G. Nigro, President L.T. Middleton, G. Serratrice, Vice-presidents Y. Shapira, Secretary L. Politano, Treasurer E. Abdel-Salam, M. Dalakas, F. Deymeer, F. Hentati, G. Meola, G. Siciliano, E. Tizzano, A. Toscano, J. Zidar Co-opted Members: V. Askanas, S. Di Mauro, K. Engel, I. Hausmanowa-Petrusewicz, R. Rüdel Acta Myologica is cited in Index Medicus/MEDLINE, Medicine, Excerpta Medica Database (EMBASE), Index Copernicus and monitored for coverage in Chemical Abstracts Service. The Journal is available on PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/journals/1221/). Journal printed with total chlorine free paper and water varnishing. Acta Myologica publishes 3 issues per year in May/July, September/October, December. Editor in Chief: Giovanni Nigro Tribunal Authorization, Napoli N. 3827, January 10, 1989 The editor remains at the complete disposal of those with rights whom it was impossible to contact, and for any omissions. Photocopies, for personal use, are permitted within the limits of 15% of each publication by following payment to SIAE of the charge due, article 68, paragraphs 4 and 5 of the Law April 22, 1941, No 633. Reproductions for professional or commercial use or for any other other purpose other than personal use can be made following a written request and specific authorization in writing from AIDRO, Corso di Porta Romana, 108, 20122 Milan, Italy, E-mail: [email protected] and web site: www.aidro.org. Publisher Via A. Gherardesca 56121 Pisa, Italy Printed by Industrie Grafiche Pacini Editore S.p.A. - Pisa - May 2014 CONTENTS INVITED REVIEW Genetic basis of limb-girdle muscular dystrophies: the 2014 update Vincenzo Nigro and Marco Savarese ............................................................ 1 ORIGINAL ARTICLE Evaluation of neural damage in Duchenne muscular dystrophy patients Ekram Abdel Salam, Iman Ehsan Abdel-Meguid, Rania Shatla and Soheir Korraa ......................... 13 CASE REPORT Limb girdle muscular dystrophy type 2L presenting as necrotizing myopathy Ilka Schneider, Gisela Stoltenburg, Marcus Deschauer, Martin Winterholler and Frank Hanisch ............... 19 2013 GAETANO CONTE PRIZE LECTURE A gating model for wildtype and R1448H Nav1.4 channels in paramyotonia Boris Holzherr, Frank Lehmann-Horn, Elza Kuzmenkina, Chunxiang Fan and Karin Jurkat-Rott ............... 22 MEMORIES BY A MYOLOGIST Vladimir Karlovich Roth (1848-1916): the founder of neuromuscular diseases studies in Russia Valery M. Kazakov, Dmitry I. Rudenko and Tima R. Stuchevskaya ...................................... 34 PROCEEDINGS OF THE XIV MEETING OF THE ITALIAN ASSOCIATION OF MYOLOGY Sirmione (BS), Italy – May 8-10, 2014 Program ................................................................................... 45 Abstracts (in alphabetical order of the 1st Author). 47 Author index ............................................................................... 79 NEWS FROM AROUND THE WORLD MSM ..................................................................................... 82 GCA ...................................................................................... 82 AIM ...................................................................................... 82 WFN ..................................................................................... 82 WMS ..................................................................................... 82 FORTHCOMING MEETINGS ............................................................... 83 Acta Myologica • 2014; XXXIII: p. 1-12 INVITED REVIEW Genetic basis of limb-girdle muscular dystrophies: the 2014 update Vincenzo Nigro and Marco Savarese Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli and Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy Limb-girdle muscular dystrophies (LGMD) are a highly het- and the respiratory muscles. The clinical course and the erogeneous group of muscle disorders, which first affect the expressivity may be variable, ranging from severe forms voluntary muscles of the hip and shoulder areas. The definition with rapid onset and progression to very mild forms al- is highly descriptive and less ambiguous by exclusion: non-X- linked, non-FSH, non-myotonic, non-distal, nonsyndromic, and lowing affected people to have fairly normal life spans non-congenital. At present, the genetic classification is becoming and activity levels (1). The term LGMD is becoming de- too complex, since the acronym LGMD has also been used for a scriptive and also comprises clinical pictures of different number of other myopathic disorders with overlapping pheno- diseases. The original definition was given as muscular types. Today, the list of genes to be screened is too large for the dystrophies milder that DMD and inherited as autosomal gene-by-gene approach and it is well suited for targeted next gen- traits (2). However, the most severe forms with child- eration sequencing (NGS) panels that should include any gene that has been so far associated with a clinical picture of LGMD. hood onset also result in dramatic physical weakness and The present review has the aim of recapitulating the genetic ba- a shortened life-span. The advent of next generation se- sis of LGMD ordering and of proposing a nomenclature for the quencing approaches has accelerated the pace of discov- orphan forms. This is useful given the pace of new discoveries. ery of new LGMD genes. Ten years ago the list included Thity-one loci have been identified so far, eight autosomal domi- 16 loci (3), while today the LGMD loci so far identified nant and 23 autosomal recessive. The dominant forms (LGMD1) are: LGMD1A (myotilin), LGMD1B (lamin A/C), LGMD1C (ca- are thirty-one, eight autosomal dominant and 23 autoso- veolin 3), LGMD1D (DNAJB6), LGMD1E (desmin), LGMD1F mal recessive. (transportin 3), LGMD1G (HNRPDL), LGMD1H (chr. 3). The autosomal recessive forms (LGMD2) are: LGMD2A (calpain 3), LGMD2B (dysferlin), LGMD2C (γ sarcoglycan), LGMD2D Autosomal dominant LGMD (α sarcoglycan), LGMD2E (β sarcoglycan), LGMD2F (δ sarco- glycan), LGMD2G (telethonin), LGMD2H (TRIM32), LGMD2I The LGMD1, i.e. the autosomal dominant forms, (FKRP), LGMD2J (titin), LGMD2K (POMT1), LGMD2L (anoc- have usually an adult-onset and are milder, because affect- tamin 5), LGMD2M (fukutin), LGMD2N (POMT2), LGMD2O ed parents are usually in quite good health at reproductive (POMTnG1), LGMD2P (dystroglycan), LGMD2Q (plectin), LG- age. They are relatively rare representing less than 10% MD2R (desmin), LGMD2S (TRAPPC11), LGMD2T (GMPPB), of all LGMD. Sometimes, they correspond to particular LGMD2U (ISPD), LGMD2V (Glucosidase, alpha ), LGMD2W cases of mutations in genes involved in other disorders, (PINCH2). such as myotilin, lamin A/C or caveolin 3 (Table 1). Key words: Limb-girdle muscular dystrophies, LGMD, NGS LGMD1A - LGMD1A may be caused by mutations in the myotilin (MYOT) gene at chr. 5q31.2. The cDNA Introduction is of 2.2 kb and contains 10 exons. Myotilin is a Z-disk- associated protein. LGMD1A may be considered as an The term limb-girdle muscular dystrophy refers to a occasional form of LGMD (4). The first clinical report long list of Mendelian disorders characterized by a pro- was in 1994 (5). The gene was identified in 2000 (6), but gressive deterioration of proximal limb muscles. Very of- myotilin mutations
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