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The TREAT-NMD DMD Global database: Analysis of More Than 7000 Duchenne Muscular Dystrophy Mutations

Catherine L. Bladen, David Salgado, Soledad Monges, Maria E. Foncuberta, Kyriaki Kekou, Konstantina Kosma, Hugh Dawkins, Leanne Lamont, Anna J. Roy, Teodora Chamova, Velina Guergueltcheva, Sophelia Chan, Lawrence Korngut, Craig Campbell, Yi Dai, Jen Wang, Nina Barišić, Petr Brabec, Jaana Lahdetie, Maggie C. Walter, Olivia Schreiber-Katz, Veronika Karcagi, Marta Garami, Venkatarman Viswanathan, Farhad Bayat, Filippo Buccella, En Kimura, Zaïda Koeks, Janneke C. van den Bergen, Miriam Rodrigues, Richard Roxburgh, Anna Lusakowska, Anna Kostera-Pruszczyk, Janusz Zimowski, Rosário Santos, Elena Neagu, Svetlana Artemieva, Vedrana Milic Rasic, Dina Vojinovic, Manuel Posada, Clemens Bloetzer, Pierre-Yves Jeannet, Franziska Joncourt, Jordi Díaz-Manera, Eduard Gallardo, A. Ayşe Karaduman, Haluk Topaloğlu, Rasha El Sherif, Angela Stringer, Andriy V. Shatillo, Ann S. Martin, Holly L. Peay, Matthew I. Bellgard, Jan Kirschner, Kevin M. Flanigan, Volker Straub, Kate Bushby, Jan Verschuuren, Annemieke Aartsma-Rus, Christophe Béroud and Hanns Lochmüller

Journal : Human Mutation, volume 36, issue 4, pages 395-402
Published : April, 2015
Category – Networking, Registries, TREAT-NMD
Disease – DMD

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease.

Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations.

Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

DOI:10.1002/humu.22758
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