The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations
Bladen, C. L., Salgado, D., Monges, S., Foncuberta, M. E., Kekou, K., Kosma, K., Dawkins, H., Lamont, L., Roy, A. J., Chamova, T., Guergueltcheva, V., Chan, S., Korngut, L., Campbell, C., Dai, Y., Wang, J., Barišić, N., Brabec, P., Lahdetie, J., Walter, M. C., Schreiber-Katz, O., Karcagi, V., Garami, M., Viswanathan, V., Bayat, F., Buccella, F., Kimura, E., Koeks, Z., van den Bergen, J. C., Rodrigues, M., Roxburgh, R., Lusakowska, A., Kostera-Pruszczyk, A., Zimowski, J., Santos, R., Neagu, E., Artemieva, S., Rasic, V. M., Vojinovic, D., Posada, M., Bloetzer, C., Jeannet, P.-Y., Joncourt, F., Díaz-Manera, J., Gallardo, E., Karaduman, A. A., Topaloğlu, H., El Sherif, R., Stringer, A., Shatillo, A. V., Martin, A. S., Peay, H. L., Bellgard, M. I., Kirschner, J., Flanigan, K. M., Straub, V., Bushby, K., Verschuuren, J., Aartsma-Rus, A., Béroud, C. and Lochmüller, H.
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).