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

International Journal of Molecular Sciences

Luz Berenice López-Hernández⁶  Benjamín Gómez-D໚z¹  Alexandra Berenice Luna-Angulo⁷  Mónica Anaya-Segura⁹  David John Bunyan⁴  Carolina Zúñiga-Guzman⁹  Rosa Elena Escobar-Cedillo¹  Bladimir Roque-Ramírez⁶  Luis Angel Ruano-Calderón²  Hຜtor Rangel-Villalobos⁵  Julia Angélica López-Hernández⁸  Francisco Javier Estrada-Mena⁷  Silvia Garc໚⁶  Ramón Mauricio Coral-Vázquez³ 

[1] National Institute of Rehabilitation, Mexico City 14389, Mexico; E-Mails:;General Hospital of Durango, Durango, 34000, Mexico; E-Mail:;Studies Section of Postgraduate and Research, School of Medicine, National Polytechnic Institute, Mexico City 11340, Mexico; E-Mail:;Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK; E-Mail:;Instituto de Investigación en Genética Molecular, Centro Universitario de la Ciénega, Universidad de Guadalajara, Ocotlán, 47810, México; E-Mail:;National Medical Centre “20 de Noviembre”, Institute for Social Security of State Workers, Mexico City 03100, Mexico; E-Mails:;Department of Molecular Biology, Panamerican University, Mexico City 03920, Mexico; E-Mails:;Department of Human Genetics, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands; E-Mail:;Asociación de Distrofia Muscular de Occidente A.C., Guadalajara 44380, Mexico; E-Mails:

关键词: Ataluren;    DMD gene;    MLPA;    exon skipping;    Duchenne;    therapies;   

DOI  :  10.3390/ijms16035334

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.