Journal Article

Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53

Politano, Luisa, Coratti, Giorgia, Battini, Roberta, Donati, Alice, Mazzone, Elena, Goemans, Nathalie, Muntoni, Francesco, Comi, Giacomo P., Ricci, Federica, Berardinelli, Angela, D’Amico, Adele, Magri, Francesca, Pane, Marika, Sansone, Valeria A., Mongini, Tiziana, Baranello, Giovanni, Bruno, Claudio, Brogna, Claudia, Previtali, Stefano C., Bertini, Enrico, Messina, Sonia, Mercuri, Eugenio, Vita, Gianluca, Pegoraro, Elena, Bello, Luca, Ricotti, Valeria

2019

Overview

The aim of this international collaborative effort was to report 36-month longitudinal changes using the 6MWT in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53. Of the 92 patients included in the study, 24 had deletions amenable to skip exon 44, 27 exon 45, 18 exon 51, and 28 exon 53. Five patients with a single deletion of exon 52 were counted in both subgroups skipping exon 51 and 53. The difference between subgroups amenable to skip different exons was not significant at 12 months but became significant at both 24 (p≤0.05) and 36 months (p≤0.01). Mutations amenable to skip exon 53 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had better results both at baseline and at follow up. Deletions amenable to skip exon 45 were associated with a more variable pattern of progression. Single exon deletions were more often associated with less drastic changes but this was not always true in individual cases. Our results confirm that the progression of disease can differ between patients with different deletions, although the changes only become significant from 24 months onwards. This information is relevant because there are current clinical trials specifically targeting patients with these subgroups of mutations.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology and Life Sciences / Child / Child, Preschool / Children & youth / Childrens health / Clinical trials / Cohort Studies / Collaboration / Disease Progression / Duchenne muscular dystrophy / Duchenne's muscular dystrophy / Dystrophin - genetics / Dystrophy / Exons / Glucocorticoids / Hospitals / Humans / Longitudinal Studies / Male / Medical research / Medicine and Health Sciences / Muscular dystrophy / Muscular Dystrophy, Duchenne - genetics / Muscular Dystrophy, Duchenne - physiopathology / Muscular Dystrophy, Duchenne - therapy / Mutation / Neurology / Neurosciences / Pediatrics / Physical Sciences / Prospective Studies / Public health / Sequence Deletion / Subgroups / Walking