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Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations.
Hum Mutat. 2009 Mar; 30(3):293-9.HM

Abstract

Antisense-mediated exon skipping aiming for reading frame restoration is currently a promising therapeutic application for Duchenne muscular dystrophy (DMD). This approach is mutation specific, but as the majority of DMD patients have deletions that cluster in hotspot regions, the skipping of a small number of exons is applicable to relatively large numbers of patients. To assess the actual applicability of the exon skipping approach, we here determined for deletions, duplications and point mutations reported in the Leiden DMD mutation database, which exon(s) should be skipped to restore the open reading frame. In theory, single and double exon skipping would be applicable to 79% of deletions, 91% of small mutations, and 73% of duplications, amounting to 83% of all DMD mutations. Exon 51 skipping, which is being tested in clinical trials, would be applicable to the largest group (13%) of all DMD patients. Further research is needed to determine the functionality of different in-frame dystrophins and a number of hurdles has to be overcome before this approach can be applied clinically.

Authors+Show Affiliations

Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. a.m.nus@lumc.nlNo 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
Review

Language

eng

PubMed ID

19156838

Citation

Aartsma-Rus, Annemieke, et al. "Theoretic Applicability of Antisense-mediated Exon Skipping for Duchenne Muscular Dystrophy Mutations." Human Mutation, vol. 30, no. 3, 2009, pp. 293-9.
Aartsma-Rus A, Fokkema I, Verschuuren J, et al. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat. 2009;30(3):293-9.
Aartsma-Rus, A., Fokkema, I., Verschuuren, J., Ginjaar, I., van Deutekom, J., van Ommen, G. J., & den Dunnen, J. T. (2009). Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Human Mutation, 30(3), 293-9. https://doi.org/10.1002/humu.20918
Aartsma-Rus A, et al. Theoretic Applicability of Antisense-mediated Exon Skipping for Duchenne Muscular Dystrophy Mutations. Hum Mutat. 2009;30(3):293-9. PubMed PMID: 19156838.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. AU - Aartsma-Rus,Annemieke, AU - Fokkema,Ivo, AU - Verschuuren,Jan, AU - Ginjaar,Ieke, AU - van Deutekom,Judith, AU - van Ommen,Gert-Jan, AU - den Dunnen,Johan T, PY - 2009/1/22/entrez PY - 2009/1/22/pubmed PY - 2009/5/29/medline SP - 293 EP - 9 JF - Human mutation JO - Hum Mutat VL - 30 IS - 3 N2 - Antisense-mediated exon skipping aiming for reading frame restoration is currently a promising therapeutic application for Duchenne muscular dystrophy (DMD). This approach is mutation specific, but as the majority of DMD patients have deletions that cluster in hotspot regions, the skipping of a small number of exons is applicable to relatively large numbers of patients. To assess the actual applicability of the exon skipping approach, we here determined for deletions, duplications and point mutations reported in the Leiden DMD mutation database, which exon(s) should be skipped to restore the open reading frame. In theory, single and double exon skipping would be applicable to 79% of deletions, 91% of small mutations, and 73% of duplications, amounting to 83% of all DMD mutations. Exon 51 skipping, which is being tested in clinical trials, would be applicable to the largest group (13%) of all DMD patients. Further research is needed to determine the functionality of different in-frame dystrophins and a number of hurdles has to be overcome before this approach can be applied clinically. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/19156838/Theoretic_applicability_of_antisense_mediated_exon_skipping_for_Duchenne_muscular_dystrophy_mutations_ L2 - https://doi.org/10.1002/humu.20918 DB - PRIME DP - Unbound Medicine ER -