The TREAT-NMD DMD global database

Analysis of more than 7,000 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 & 41 others Olivia Schreiber-Katz, V. 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

Research output: Contribution to journalArticle

158 Citations (Scopus)

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).

Original languageEnglish
Pages (from-to)395-402
Number of pages8
JournalHuman Mutation
Volume36
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Duchenne Muscular Dystrophy
Databases
Mutation
Exons
Inborn Genetic Diseases
Terminator Codon
Nonsense Codon
Missense Mutation
Point Mutation
Genetic Therapy

Keywords

  • DMD
  • Duchenne muscular dystrophy
  • Rare disease registries
  • TREAT-NMD

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Bladen, C. L., Salgado, D., Monges, S., Foncuberta, M. E., Kekou, K., Kosma, K., ... Lochmüller, H. (2015). The TREAT-NMD DMD global database: Analysis of more than 7,000 duchenne muscular dystrophy mutations. Human Mutation, 36(4), 395-402. https://doi.org/10.1002/humu.22758

The TREAT-NMD DMD global database : Analysis of more than 7,000 duchenne muscular dystrophy mutations. / Bladen, Catherine L.; Salgado, David; Monges, Soledad; Foncuberta, Maria E.; Kekou, Kyriaki; Kosma, Konstantina; Dawkins, Hugh; Lamont, Leanne; Roy, Anna J.; Chamova, Teodora; Guergueltcheva, Velina; Chan, Sophelia; Korngut, Lawrence; Campbell, Craig; Dai, Yi; Wang, Jen; Barišić, Nina; Brabec, Petr; Lahdetie, Jaana; Walter, Maggie C.; Schreiber-Katz, Olivia; Karcagi, V.; Garami, Marta; Viswanathan, Venkatarman; Bayat, Farhad; Buccella, Filippo; Kimura, En; Koeks, Zaïda; van den Bergen, Janneke C.; Rodrigues, Miriam; Roxburgh, Richard; Lusakowska, Anna; Kostera-Pruszczyk, Anna; Zimowski, Janusz; Santos, Rosário; Neagu, Elena; Artemieva, Svetlana; Rasic, Vedrana Milic; Vojinovic, Dina; Posada, Manuel; Bloetzer, Clemens; Jeannet, Pierre Yves; Joncourt, Franziska; Díaz-Manera, Jordi; Gallardo, Eduard; Karaduman, A. Ayşe; Topaloğlu, Haluk; El Sherif, Rasha; Stringer, Angela; Shatillo, Andriy V.; Martin, Ann S.; Peay, Holly L.; Bellgard, Matthew I.; Kirschner, Jan; Flanigan, Kevin M.; Straub, Volker; Bushby, Kate; Verschuuren, Jan; Aartsma-Rus, Annemieke; Béroud, Christophe; Lochmüller, Hanns.

In: Human Mutation, Vol. 36, No. 4, 01.04.2015, p. 395-402.

Research output: Contribution to journalArticle

Bladen, CL, Salgado, D, Monges, S, Foncuberta, ME, Kekou, K, Kosma, K, Dawkins, H, Lamont, L, Roy, AJ, Chamova, T, Guergueltcheva, V, Chan, S, Korngut, L, Campbell, C, Dai, Y, Wang, J, Barišić, N, Brabec, P, Lahdetie, J, Walter, MC, Schreiber-Katz, O, Karcagi, V, Garami, M, Viswanathan, V, Bayat, F, Buccella, F, Kimura, E, Koeks, Z, van den Bergen, JC, Rodrigues, M, Roxburgh, R, Lusakowska, A, Kostera-Pruszczyk, A, Zimowski, J, Santos, R, Neagu, E, Artemieva, S, Rasic, VM, Vojinovic, D, Posada, M, Bloetzer, C, Jeannet, PY, Joncourt, F, Díaz-Manera, J, Gallardo, E, Karaduman, AA, Topaloğlu, H, El Sherif, R, Stringer, A, Shatillo, AV, Martin, AS, Peay, HL, Bellgard, MI, Kirschner, J, Flanigan, KM, Straub, V, Bushby, K, Verschuuren, J, Aartsma-Rus, A, Béroud, C & Lochmüller, H 2015, 'The TREAT-NMD DMD global database: Analysis of more than 7,000 duchenne muscular dystrophy mutations', Human Mutation, vol. 36, no. 4, pp. 395-402. https://doi.org/10.1002/humu.22758
Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K et al. The TREAT-NMD DMD global database: Analysis of more than 7,000 duchenne muscular dystrophy mutations. Human Mutation. 2015 Apr 1;36(4):395-402. https://doi.org/10.1002/humu.22758
Bladen, Catherine L. ; Salgado, David ; Monges, Soledad ; Foncuberta, Maria E. ; Kekou, Kyriaki ; Kosma, Konstantina ; Dawkins, Hugh ; Lamont, Leanne ; Roy, Anna J. ; Chamova, Teodora ; Guergueltcheva, Velina ; Chan, Sophelia ; Korngut, Lawrence ; Campbell, Craig ; Dai, Yi ; Wang, Jen ; Barišić, Nina ; Brabec, Petr ; Lahdetie, Jaana ; Walter, Maggie C. ; Schreiber-Katz, Olivia ; Karcagi, V. ; Garami, Marta ; Viswanathan, Venkatarman ; Bayat, Farhad ; Buccella, Filippo ; Kimura, En ; Koeks, Zaïda ; van den Bergen, Janneke C. ; Rodrigues, Miriam ; Roxburgh, Richard ; Lusakowska, Anna ; Kostera-Pruszczyk, Anna ; Zimowski, Janusz ; Santos, Rosário ; Neagu, Elena ; Artemieva, Svetlana ; Rasic, Vedrana Milic ; Vojinovic, Dina ; Posada, Manuel ; Bloetzer, Clemens ; Jeannet, Pierre Yves ; Joncourt, Franziska ; Díaz-Manera, Jordi ; Gallardo, Eduard ; Karaduman, A. Ayşe ; Topaloğlu, Haluk ; El Sherif, Rasha ; Stringer, Angela ; Shatillo, Andriy V. ; Martin, Ann S. ; Peay, Holly L. ; Bellgard, Matthew I. ; Kirschner, Jan ; Flanigan, Kevin M. ; Straub, Volker ; Bushby, Kate ; Verschuuren, Jan ; Aartsma-Rus, Annemieke ; Béroud, Christophe ; Lochmüller, Hanns. / The TREAT-NMD DMD global database : Analysis of more than 7,000 duchenne muscular dystrophy mutations. In: Human Mutation. 2015 ; Vol. 36, No. 4. pp. 395-402.
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AU - Bladen, Catherine L.

AU - Salgado, David

AU - Monges, Soledad

AU - Foncuberta, Maria E.

AU - Kekou, Kyriaki

AU - Kosma, Konstantina

AU - Dawkins, Hugh

AU - Lamont, Leanne

AU - Roy, Anna J.

AU - Chamova, Teodora

AU - Guergueltcheva, Velina

AU - Chan, Sophelia

AU - Korngut, Lawrence

AU - Campbell, Craig

AU - Dai, Yi

AU - Wang, Jen

AU - Barišić, Nina

AU - Brabec, Petr

AU - Lahdetie, Jaana

AU - Walter, Maggie C.

AU - Schreiber-Katz, Olivia

AU - Karcagi, V.

AU - Garami, Marta

AU - Viswanathan, Venkatarman

AU - Bayat, Farhad

AU - Buccella, Filippo

AU - Kimura, En

AU - Koeks, Zaïda

AU - van den Bergen, Janneke C.

AU - Rodrigues, Miriam

AU - Roxburgh, Richard

AU - Lusakowska, Anna

AU - Kostera-Pruszczyk, Anna

AU - Zimowski, Janusz

AU - Santos, Rosário

AU - Neagu, Elena

AU - Artemieva, Svetlana

AU - Rasic, Vedrana Milic

AU - Vojinovic, Dina

AU - Posada, Manuel

AU - Bloetzer, Clemens

AU - Jeannet, Pierre Yves

AU - Joncourt, Franziska

AU - Díaz-Manera, Jordi

AU - Gallardo, Eduard

AU - Karaduman, A. Ayşe

AU - Topaloğlu, Haluk

AU - El Sherif, Rasha

AU - Stringer, Angela

AU - Shatillo, Andriy V.

AU - Martin, Ann S.

AU - Peay, Holly L.

AU - Bellgard, Matthew I.

AU - Kirschner, Jan

AU - Flanigan, Kevin M.

AU - Straub, Volker

AU - Bushby, Kate

AU - Verschuuren, Jan

AU - Aartsma-Rus, Annemieke

AU - Béroud, Christophe

AU - Lochmüller, Hanns

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KW - Duchenne muscular dystrophy

KW - Rare disease registries

KW - TREAT-NMD

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