Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies

Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2015
Author(s)
López-Hernández, Luz Berenice
Gómez-Díaz, Benjamín
Luna-Angulo, Alexandra
Anaya-Segura, Mónica
Bunyan, David John
Zúñiga-Guzman, Carolina
Escobar-Cedillo, Rosa
Roque-Ramírez, Bladimir
Ruano-Calderón, Luis
Rangel-Villalobos, Héctor
López-Hernández, Julia Angélica
García, Silvia
Coral-Vázquez, Ramón
Type
text::journal::journal article
DOI
URL
Abstract
Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.