title: Comparison of mutation profiles in the Duchenne muscular dystrophy gene among populations: implications for potential molecular therapies.
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.
authors.affiliation: National Medical Centre "20 de Noviembre", Institute for Social Security of State Workers, Mexico City 03100, Mexico. lblhmedgen@gmail.com.|Asociación de Distrofia Muscular de Occidente A.C., Guadalajara 44380, Mexico. lblhmedgen@gmail.com.
authors.forename: Luz Berenice
authors.initials: LB
authors.lastname: López-Hernández
authors.affiliation: National Institute of Rehabilitation, Mexico City 14389, Mexico.
authors.forename: Benjamín
authors.initials: B
authors.lastname: Gómez-Díaz
authors.affiliation: Department of Molecular Biology, Panamerican University, Mexico City 03920, Mexico.
authors.forename: Alexandra Berenice
authors.initials: AB
authors.lastname: Luna-Angulo
authors.affiliation: Asociación de Distrofia Muscular de Occidente A.C., Guadalajara 44380, Mexico.|University Center of Exact Sciences and Engineering, University of Guadalajara, Guadalajara 44430, Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Anaya-Segura
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK. Dave.Bunyan@salisbury.nhs.uk.
authors.forename: David John
authors.initials: DJ
authors.lastname: Bunyan
authors.affiliation: Asociación de Distrofia Muscular de Occidente A.C., Guadalajara 44380, Mexico. anilorac_zg911@hotmail.com.|University Center of Exact Sciences and Engineering, University of Guadalajara, Guadalajara 44430, Mexico. anilorac_zg911@hotmail.com.
authors.forename: Carolina
authors.initials: C
authors.lastname: Zúñiga-Guzman
authors.affiliation: National Institute of Rehabilitation, Mexico City 14389, Mexico.
authors.forename: Rosa Elena
authors.initials: RE
authors.lastname: Escobar-Cedillo
authors.affiliation: National Medical Centre "20 de Noviembre", Institute for Social Security of State Workers, Mexico City 03100, Mexico. bladimir_roque@hotmail.com.
authors.forename: Bladimir
authors.initials: B
authors.lastname: Roque-Ramírez
authors.affiliation: General Hospital of Durango, Durango, 34000, Mexico. laruanoc@hotmail.com.
authors.forename: Luis Angel
authors.initials: LA
authors.lastname: Ruano-Calderón
authors.affiliation: Instituto de Investigación en Genética Molecular, Centro Universitario de la Ciénega, Universidad de Guadalajara, Ocotlán, 47810, México. hrangel13@hotmail.com.
authors.forename: Héctor
authors.initials: H
authors.lastname: Rangel-Villalobos
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands. julyberries@hotmail.com.
authors.forename: Julia Angélica
authors.initials: JA
authors.lastname: López-Hernández
authors.affiliation: Department of Molecular Biology, Panamerican University, Mexico City 03920, Mexico.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Estrada-Mena
authors.affiliation: National Medical Centre "20 de Noviembre", Institute for Social Security of State Workers, Mexico City 03100, Mexico. rolasil@yahoo.com.mx.
authors.forename: Silvia
authors.initials: S
authors.lastname: García
authors.affiliation: Studies Section of Postgraduate and Research, School of Medicine, National Polytechnic Institute, Mexico City 11340, Mexico.
authors.forename: Ramón Mauricio
authors.initials: RM
authors.lastname: Coral-Vázquez
mesh_terms: D016189:Dystrophin / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D015316:Genetic Therapy; D006801:Humans; D008800:Mexico; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000628:therapy; D009154:Mutation
chemical_list: C484258:DMD protein, human; D016189:Dystrophin