Περίληψη:
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). © 2015 The Authors.
Συγγραφείς:
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.
Lochmüller, H.
