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. 2015 Apr;36(4):395-402.
doi: 10.1002/humu.22758. Epub 2015 Mar 17.

The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations

Catherine L Bladen  1 , 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, Hanns Lochmüller
Affiliations

The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations

Catherine L Bladen et al. Hum Mutat. 2015 Apr.

Abstract

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).

Keywords: DMD; Duchenne muscular dystrophy; TREAT-NMD; rare disease registries.

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Figures

Figure 1
Figure 1
Upload of data from national TREAT-NMD DMD registries to Global database. Standardized aggregate data from the national TREAT-NMD DMD registries was transferred to the global DMD database via a secure File Transfer Protocol transfer in order to provide a single cohort of genetic and clinical variants.
Figure 2
Figure 2
Most commonly reported large mutations. Most commonly reported large deletions (recorded 100 times or more) (A) and large duplications (recorded ten times or more) (B) in the TREAT-NMD DMD Global database.
Figure 3
Figure 3
Distribution of the most common large deletions and duplications on the DMD gene.
Figure 4
Figure 4
Geography and DMD mutations. Distribution of DMD mutation types stratified by continent.
See this image and copyright information in PMC

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