The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations
Catherine Bladen
,
David Salgado
(1)
,
Soledad Monges
(2)
,
Maria E Foncuberta
,
Kyriaki Kekou
,
Konstantina Kosma
,
Hugh Dawkins
(3)
,
Leanne Lamont
,
Anna Roy
,
Teodora Chamova
,
Velina Guergueltcheva
,
Sophelia Chan
,
Lawrence Korngut
,
Craig Campbell
,
Yi Dai
,
Jen Wang
,
Nina Barišić
,
Petr Brabec
,
Jaana Lahdetie
,
Maggie C Walter
(4)
,
Olivia Schreiber-Katz
,
Veronika Karcagi
,
Marta Garami
,
Venkatarman Viswanathan
,
Farhad Bayat
,
Filippo Buccella
,
En Kimura
,
Zaïda Koeks
,
Jan van den Bergen
,
Miriam Rodrigues
,
Richard Roxburgh
,
Anna Lusakowska
(5)
,
Anna Kostera-Pruszczyk
,
Jan Zimowski
,
Rosário Santos
,
Elena Neagu
,
Svetlana Artemieva
,
Vedrana Milic Rasic
,
Dina Vojinovic
,
Manuel Posada
(6)
,
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
(7)
,
Kate Bushby
(7)
,
Jan Verschuuren
,
Annemieke Aartsma-Rus
(8)
,
Christophe Béroud
(1)
,
Hanns Lochmuller
(9)
,
Maria E. Foncuberta
,
Maggie C. Walter
,
A. Ayşe Karaduman
,
Andriy V. Shatillo
,
Ann S. Martin
,
Holly L. Peay
,
Matthew I. Bellgard
,
Kevin M. Flanigan
1
GMGF -
Génétique Médicale et Génomique Fonctionnelle
2 Neuropaediatrics
3 Centre for Comparative Genomics
4 Department of Biological and Environmental Engineering
5 Department of Embryology [Warsaw]
6 Medicina Pediátrica y del Desarrollo
7 Department of Neurology
8 Human Genetics
9 Newcastle University [Newcastle]
2 Neuropaediatrics
3 Centre for Comparative Genomics
4 Department of Biological and Environmental Engineering
5 Department of Embryology [Warsaw]
6 Medicina Pediátrica y del Desarrollo
7 Department of Neurology
8 Human Genetics
9 Newcastle University [Newcastle]
Catherine Bladen
- Function : Author
David Salgado
- Function : Author
- PersonId : 16191
- IdHAL : david-salgado
- ORCID : 0000-0002-5905-3591
- IdRef : 139792147
Maria E Foncuberta
- Function : Author
Kyriaki Kekou
- Function : Author
Konstantina Kosma
- Function : Author
Leanne Lamont
- Function : Author
Anna Roy
- Function : Author
Teodora Chamova
- Function : Author
Velina Guergueltcheva
- Function : Author
Sophelia Chan
- Function : Author
Lawrence Korngut
- Function : Author
Craig Campbell
- Function : Author
Yi Dai
- Function : Author
Jen Wang
- Function : Author
Nina Barišić
- Function : Author
Petr Brabec
- Function : Author
Jaana Lahdetie
- Function : Author
Olivia Schreiber-Katz
- Function : Author
Veronika Karcagi
- Function : Author
Marta Garami
- Function : Author
Venkatarman Viswanathan
- Function : Author
Farhad Bayat
- Function : Author
Filippo Buccella
- Function : Author
En Kimura
- Function : Author
Zaïda Koeks
- Function : Author
Jan van den Bergen
- Function : Author
Miriam Rodrigues
- Function : Author
Richard Roxburgh
- Function : Author
Anna Lusakowska
- Function : Author
- PersonId : 764193
- ORCID : 0000-0003-1909-9963
Anna Kostera-Pruszczyk
- Function : Author
Jan Zimowski
- Function : Author
Rosário Santos
- Function : Author
Elena Neagu
- Function : Author
Svetlana Artemieva
- Function : Author
Vedrana Milic Rasic
- Function : Author
Dina Vojinovic
- Function : Author
Clemens Bloetzer
- Function : Author
Pierre-Yves Jeannet
- Function : Author
Franziska Joncourt
- Function : Author
Jordi Díaz-Manera
- Function : Author
Eduard Gallardo
- Function : Author
a Ayşe Karaduman
- Function : Author
Haluk Topaloğlu
- Function : Author
Rasha El Sherif
- Function : Author
Angela Stringer
- Function : Author
Andriy V Shatillo
- Function : Author
Ann S Martin
- Function : Author
Holly L Peay
- Function : Author
Matthew I Bellgard
- Function : Author
Jan Kirschner
- Function : Author
Kevin M Flanigan
- Function : Author
Jan Verschuuren
- Function : Author
Christophe Béroud
- Function : Author
- PersonId : 16989
- IdHAL : christophe-beroud
- ORCID : 0000-0003-2986-8738
- IdRef : 155036343
Maria E. Foncuberta
- Function : Author
Maggie C. Walter
- Function : Author
A. Ayşe Karaduman
- Function : Author
Andriy V. Shatillo
- Function : Author
Ann S. Martin
- Function : Author
Holly L. Peay
- Function : Author
Matthew I. Bellgard
- Function : Author
Kevin M. Flanigan
- Function : Author
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).