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Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy.
Hum Mutat. 2007 Feb; 28(2):196-202.HM

Abstract

Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show intragenic deletions ranging from one to several exons of the DMD gene and leading to a premature stop codon. Other deletions that maintain the translational reading frame of the gene result in the milder Becker muscular dystrophy (BMD) form of the disease. Thus the opportunity to transform a DMD phenotype into a BMD phenotype appeared as a new treatment strategy with the development of antisense oligonucleotides technology, which is able to induce an exon skipping at the pre-mRNA level in order to restore an open reading frame. Because the DMD gene contains 79 exons, thousands of potential transcripts could be produced by exon skipping and should be investigated. The conventional approach considers skipping of a single exon. Here we report the comparison of single- and multiple-exon skipping strategies based on bioinformatic analysis. By using the Universal Mutation Database (UMD)-DMD, we predict that an optimal multiexon skipping leading to the del45-55 artificial dystrophin (c.6439_8217del) could transform the DMD phenotype into the asymptomatic or mild BMD phenotype. This multiple-exon skipping could theoretically rescue up to 63% of DMD patients with a deletion, while the optimal monoskipping of exon 51 would rescue only 16% of patients.

Authors+Show Affiliations

Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Unité de Formation et de Recherche Médecine Site Nord Unité Pédagogique Médicale/IURC, Montpellier, France. christophe.beroud@igh.cnrs.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17041910

Citation

Béroud, Christophe, et al. "Multiexon Skipping Leading to an Artificial DMD Protein Lacking Amino Acids From Exons 45 Through 55 Could Rescue Up to 63% of Patients With Duchenne Muscular Dystrophy." Human Mutation, vol. 28, no. 2, 2007, pp. 196-202.
Béroud C, Tuffery-Giraud S, Matsuo M, et al. Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy. Hum Mutat. 2007;28(2):196-202.
Béroud, C., Tuffery-Giraud, S., Matsuo, M., Hamroun, D., Humbertclaude, V., Monnier, N., Moizard, M. P., Voelckel, M. A., Calemard, L. M., Boisseau, P., Blayau, M., Philippe, C., Cossée, M., Pagès, M., Rivier, F., Danos, O., Garcia, L., & Claustres, M. (2007). Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy. Human Mutation, 28(2), 196-202.
Béroud C, et al. Multiexon Skipping Leading to an Artificial DMD Protein Lacking Amino Acids From Exons 45 Through 55 Could Rescue Up to 63% of Patients With Duchenne Muscular Dystrophy. Hum Mutat. 2007;28(2):196-202. PubMed PMID: 17041910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy. AU - Béroud,Christophe, AU - Tuffery-Giraud,Sylvie, AU - Matsuo,Masafumi, AU - Hamroun,Dalil, AU - Humbertclaude,Véronique, AU - Monnier,Nicole, AU - Moizard,Marie-Pierre, AU - Voelckel,Marie-Antoinette, AU - Calemard,Laurence Michel, AU - Boisseau,Pierre, AU - Blayau,Martine, AU - Philippe,Christophe, AU - Cossée,Mireille, AU - Pagès,Michel, AU - Rivier,François, AU - Danos,Olivier, AU - Garcia,Luis, AU - Claustres,Mireille, PY - 2006/10/17/pubmed PY - 2007/3/1/medline PY - 2006/10/17/entrez SP - 196 EP - 202 JF - Human mutation JO - Hum Mutat VL - 28 IS - 2 N2 - Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show intragenic deletions ranging from one to several exons of the DMD gene and leading to a premature stop codon. Other deletions that maintain the translational reading frame of the gene result in the milder Becker muscular dystrophy (BMD) form of the disease. Thus the opportunity to transform a DMD phenotype into a BMD phenotype appeared as a new treatment strategy with the development of antisense oligonucleotides technology, which is able to induce an exon skipping at the pre-mRNA level in order to restore an open reading frame. Because the DMD gene contains 79 exons, thousands of potential transcripts could be produced by exon skipping and should be investigated. The conventional approach considers skipping of a single exon. Here we report the comparison of single- and multiple-exon skipping strategies based on bioinformatic analysis. By using the Universal Mutation Database (UMD)-DMD, we predict that an optimal multiexon skipping leading to the del45-55 artificial dystrophin (c.6439_8217del) could transform the DMD phenotype into the asymptomatic or mild BMD phenotype. This multiple-exon skipping could theoretically rescue up to 63% of DMD patients with a deletion, while the optimal monoskipping of exon 51 would rescue only 16% of patients. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/17041910/Multiexon_skipping_leading_to_an_artificial_DMD_protein_lacking_amino_acids_from_exons_45_through_55_could_rescue_up_to_63_of_patients_with_Duchenne_muscular_dystrophy_ L2 - https://doi.org/10.1002/humu.20428 DB - PRIME DP - Unbound Medicine ER -