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Theoretic applicability of antisense‐mediated exon skipping for Duchenne muscular dystrophy mutations
Author(s) -
AartsmaRus Annemieke,
Fokkema Ivo,
Verschuuren Jan,
Ginjaar Ieke,
van Deutekom Judith,
van Ommen GertJan,
den Dunnen Johan T.
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20918
Subject(s) - exon , exon skipping , duchenne muscular dystrophy , biology , genetics , point mutation , muscular dystrophy , mutation , open reading frame , dystrophin , computational biology , bioinformatics , gene , alternative splicing , peptide sequence
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. Hum Mutat 0, 1–7, 2009. © 2009 Wiley‐Liss, Inc.