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PLoS One. 2019 Jun 25;14(6):e0218683. doi: 10.1371/journal.pone.0218683. eCollection 2019.

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

Author information

1
Pediatric Neurology, Department of Woman and Child Health and Public Health, Child Health Area, Università Cattolica del Sacro Cuore, Rome, Italy.
2
Centro Clinico Nemo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
3
Dubowitz Neuromuscular Centre, UCL & Great Ormond Street Hospital, London, United Kingdom.
4
NIHR Great Ormond Street Hospital Biomedical Research Centre, London, United Kingdom.
5
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
6
Nemo SUD Clinical Centre, University Hospital "G. Martino", Messina, Italy.
7
Department of Neurosciences, Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children's Hospital, Rome, Italy.
8
Center of Myology and Neurodegenerative Disorders, Istituto Giannina Gaslini, Genoa, Italy.
9
Child Neurology and Psychiatry Unit, ''Casimiro Mondino" Foundation, Pavia, Italy.
10
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
11
Neuromuscular Center, AOU Città della Salute e della Scienza, University of Torino, Torino, Italy.
12
Department of Developmental Neuroscience, Stella Maris Institute, Pisa, Italy.
13
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
14
Department of Neurosciences, University of Padua, Padua, Italy.
15
Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
16
Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
17
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli, Napoli, Italy.
18
The NEMO Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, Milan, Italy.
19
Metabolic Unit, A. Meyer Children's Hospital, Florence, Italy.
20
Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium.

Abstract

INTRODUCTION:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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).

DISCUSSION:

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.

CONCLUSION:

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

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