Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase.
UMD-DMD France is a knowledgebase developed through a multicenter academic effort to provide an up-to-date resource of curated information covering all identified mutations in patients with a dystrophinopathy. The current release includes 2,411 entries consisting in 2,084 independent mutational events identified in 2,046 male patients and 38 expressing females, which corresponds to an estimated number of 39 people per million with a genetic diagnosis of dystrophinopathy in France. Mutations consist in 1,404 large deletions, 215 large duplications, and 465 small rearrangements, of which 39.8% are nonsense mutations. The reading frame rule holds true for 96% of the DMD patients and 93% of the BMD patients. Quality control relies on the curation by four experts for the DMD gene and related diseases. Data on dystrophin and RNA analysis, phenotypic groups, and transmission are also available. About 24% of the mutations are de novo events. This national centralized resource will contribute to a greater understanding of prevalence of dystrophinopathies in France, and in particular, of the true frequency of BMD, which was found to be almost half (43%) that of DMD. UMD-DMD is a searchable anonymous database that includes numerous newly developed tools, which can benefit to all the scientific community interested in dystrophinopathies. Dedicated functions for genotype-based therapies allowed the prediction of a new multiexon skipping (del 45-53) potentially applicable to 53% of the deleted DMD patients. Finally, such a national database will prove to be useful to implement the international global DMD patients' registries under development.
Tuffery-Giraud
Sylvie
S
Université Montpellier 1, Faculté de Médecine, Montpellier, France. sylvie.tuffery@inserm.fr
Béroud
Christophe
C
Leturcq
France
F
Yaou
Rabah Ben
RB
Hamroun
Dalil
D
Michel-Calemard
Laurence
L
Moizard
Marie-Pierre
MP
Bernard
Rafaëlle
R
Cossée
Mireille
M
Boisseau
Pierre
P
Blayau
Martine
M
Creveaux
Isabelle
I
Guiochon-Mantel
Anne
A
de Martinville
Bérengère
B
Philippe
Christophe
C
Monnier
Nicole
N
Bieth
Eric
E
Khau Van Kien
Philippe
P
Desmet
François-Olivier
FO
Humbertclaude
Véronique
V
Kaplan
Jean-Claude
JC
Chelly
Jamel
J
Claustres
Mireille
M
D019457:Chromosome Breakage; D018389:Codon, Nonsense / Q000235:genetics; D030541:Databases, Genetic; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005602:France; D015321:Gene Rearrangement; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D051188:Knowledge Bases; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012984:Software
D018389:Codon, Nonsense; D016189:Dystrophin; D022821:RNA Splice Sites