. 2025 Oct;67(10):1280-1289.

doi: 10.1111/dmcn.16282. Epub 2025 Mar 14.

Dystrophin isoform deficiency and upper-limb and respiratory function in Duchenne muscular dystrophy

Mary Chesshyre¹, Deborah Ridout², Georgia Stimpson¹, Valeria Ricotti^{1

3

4}, Silvana De Lucia⁵, Erik H Niks⁶, Volker Straub^{7

8}, Laurent Servais^{9

10

11}, Jean-Yves Hogrel¹², Giovanni Baranello¹, Adnan Manzur¹; UK NorthStar Clinical Network; Francesco Muntoni^{1

3

4}; iMDEX Network

Collaborators, Affiliations

Collaborators

iMDEX Network:
Joana Domingos, Victoria Selby, Amy Wolfe, Lianne Abbott, Efthymia Panagiotopoulou, Mario Iodice, Maria Ash, Imelda de Groot, Merel Jansen, Maaike Pelsma, Marian Bobbert, Menno Van Der Holst, Yvonne D Krom, Marjolein J van Heur-Neuman, Thomas Voit, Valérie Decostre, Stéphanie Gilabert, Michela Guglieri, Alexander Murphy, Anna Mayhew, Mariacristina Scoto, Anna Sarkozy, Pinki Munot, Stephanie Robb, Elaine Chan, V Robinson, W Girshab, V Crook, E Milev, L Abbott, A Wolfe, E O'Reilly, J Watts-When, N Burnett, R Thomas, R Terespolsky, O Martinaeu, J Longatto, C Bettolo, M Guglieri, J Diaz-Manera, G Tasca, M Elseed, R Muni-Lofra, M James, D Moat, J Sodhi, K Wong, E Robinson, E Groves, R Rabb, H McMurchie, H Chase, Tracey Willis, C Rylance, N Birchall, E Wright, A Childs, K Pysden, C Martos, D Roberts, L Pallant, S Walker, A Henderson, R Madhu, R Karuvattil, Y Balla, S Gregson, S Clark, E Wraige, H Jungbluth, V Gowda, M Vanegas, J Sheehan, A Schofield, C Smith, I Hughes, E Whitehouse, S Warner, E Reading, N Emery, J Moustoukas, K Strachan, M Ong, M Atherton, N Mills, S Sanchez Marco, A Saxena, K Skone, J TeWaterNaude, H Davis, C Wood, A Majumdar, A Murugan, I Guarino, R Tomlinson, H Jarvis, L Wills, C Frimpong, J Watson, G Cobb, G Robertson, P Brink, J Burslem, C Adams, J Wong, S Joseph, I Horrocks, J Dunne, M DiMarco, S Brown, S McKenzie, K Torne, R Mohamed, V Velmurugan, M Prasad, S Sedehizadeh, A Schugal, R Keetley, S Williamson, K Payne, E Dowling, P Fenty, C de Goede, A Parkes, K Baxter, M Illingworth, N Bhangu, S Geary, J Palmer, K Shill, S Tirupathi, A Shah, D O'Donogue, J McVeigh, J McFetridge, G Nicfhirleinn, H Beattie, T Leyland, K Stevenson, N Hussain, D Baskaran, Z Lambat, R Sullivan, L Locke, G Ambegaonkar, D Krishnakumar, J Taylor, J Moores, E Stephen, J Tewnion, S Ramdas, M Sa, A Skippen, M Khries, C Lilien, H Ramjattan, F Taylor, H English, K Stewart, F Flint, E Bartram, R Noble

Affiliations

¹ Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK.
² Population, Policy and Practice Research and Teaching Department, UCL GOS Institute of Child Health, London, UK.
³ NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, UCL, London, UK.
⁴ Great Ormond Street Hospital NHS Foundation Trust, London, UK.
⁵ AP-HP, Sorbonne University, Institute of Myology, AFM-Telethon, I-Motion Pediatric Clinical Trials Platform, Armand Trousseau Hospital, Paris, France.
⁶ Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
⁷ The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁸ NIHR Newcastle Biomedical Research Centre, University of Newcastle, Newcastle upon Tyne, UK.
⁹ Centre de Référence Des Maladies Neuromusculaires, CHU de Liège, University of Liège, Liège, Belgium.
¹⁰ Department of Paediatrics, MDUK Oxford Neuromuscular Centre, Oxford, UK.
¹¹ NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
¹² Institute of Myology, Paris, France.

PMID: 40084496
PMCID: PMC12426305
DOI: 10.1111/dmcn.16282

Dystrophin isoform deficiency and upper-limb and respiratory function in Duchenne muscular dystrophy

Mary Chesshyre et al. Dev Med Child Neurol. 2025 Oct.

. 2025 Oct;67(10):1280-1289.

doi: 10.1111/dmcn.16282. Epub 2025 Mar 14.

Authors

Collaborators

iMDEX Network:
Joana Domingos, Victoria Selby, Amy Wolfe, Lianne Abbott, Efthymia Panagiotopoulou, Mario Iodice, Maria Ash, Imelda de Groot, Merel Jansen, Maaike Pelsma, Marian Bobbert, Menno Van Der Holst, Yvonne D Krom, Marjolein J van Heur-Neuman, Thomas Voit, Valérie Decostre, Stéphanie Gilabert, Michela Guglieri, Alexander Murphy, Anna Mayhew, Mariacristina Scoto, Anna Sarkozy, Pinki Munot, Stephanie Robb, Elaine Chan, V Robinson, W Girshab, V Crook, E Milev, L Abbott, A Wolfe, E O'Reilly, J Watts-When, N Burnett, R Thomas, R Terespolsky, O Martinaeu, J Longatto, C Bettolo, M Guglieri, J Diaz-Manera, G Tasca, M Elseed, R Muni-Lofra, M James, D Moat, J Sodhi, K Wong, E Robinson, E Groves, R Rabb, H McMurchie, H Chase, Tracey Willis, C Rylance, N Birchall, E Wright, A Childs, K Pysden, C Martos, D Roberts, L Pallant, S Walker, A Henderson, R Madhu, R Karuvattil, Y Balla, S Gregson, S Clark, E Wraige, H Jungbluth, V Gowda, M Vanegas, J Sheehan, A Schofield, C Smith, I Hughes, E Whitehouse, S Warner, E Reading, N Emery, J Moustoukas, K Strachan, M Ong, M Atherton, N Mills, S Sanchez Marco, A Saxena, K Skone, J TeWaterNaude, H Davis, C Wood, A Majumdar, A Murugan, I Guarino, R Tomlinson, H Jarvis, L Wills, C Frimpong, J Watson, G Cobb, G Robertson, P Brink, J Burslem, C Adams, J Wong, S Joseph, I Horrocks, J Dunne, M DiMarco, S Brown, S McKenzie, K Torne, R Mohamed, V Velmurugan, M Prasad, S Sedehizadeh, A Schugal, R Keetley, S Williamson, K Payne, E Dowling, P Fenty, C de Goede, A Parkes, K Baxter, M Illingworth, N Bhangu, S Geary, J Palmer, K Shill, S Tirupathi, A Shah, D O'Donogue, J McVeigh, J McFetridge, G Nicfhirleinn, H Beattie, T Leyland, K Stevenson, N Hussain, D Baskaran, Z Lambat, R Sullivan, L Locke, G Ambegaonkar, D Krishnakumar, J Taylor, J Moores, E Stephen, J Tewnion, S Ramdas, M Sa, A Skippen, M Khries, C Lilien, H Ramjattan, F Taylor, H English, K Stewart, F Flint, E Bartram, R Noble

Affiliations

¹ Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK.
² Population, Policy and Practice Research and Teaching Department, UCL GOS Institute of Child Health, London, UK.
³ NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, UCL, London, UK.
⁴ Great Ormond Street Hospital NHS Foundation Trust, London, UK.
⁵ AP-HP, Sorbonne University, Institute of Myology, AFM-Telethon, I-Motion Pediatric Clinical Trials Platform, Armand Trousseau Hospital, Paris, France.
⁶ Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
⁷ The John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁸ NIHR Newcastle Biomedical Research Centre, University of Newcastle, Newcastle upon Tyne, UK.
⁹ Centre de Référence Des Maladies Neuromusculaires, CHU de Liège, University of Liège, Liège, Belgium.
¹⁰ Department of Paediatrics, MDUK Oxford Neuromuscular Centre, Oxford, UK.
¹¹ NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
¹² Institute of Myology, Paris, France.

PMID: 40084496
PMCID: PMC12426305
DOI: 10.1111/dmcn.16282

Abstract

Aim: To investigate the associations between mutations expected to differentially affect Dp140 expression and long-term trajectories of respiratory and upper-limb motor outcomes in Duchenne muscular dystrophy (DMD).

Method: In a retrospective analysis of population-based longitudinal data from three real-world and natural history data sources, individuals with DMD aged 5 years to 18 years were subdivided according to the predicted effects of the participants' DMD mutation on dystrophin isoform expression (group 1, Dp427 absent, Dp140/Dp71 present; group 2, Dp427/Dp140 absent, Dp71 present).

Results: A total of 459 participants were studied, with upper-limb outcomes assessed in 71 (27 in group 1 and 44 in group 2) and forced vital capacity percentage predicted (%pred) assessed in 434 (224 in group 1 and 210 in group 2). Mean grip strength %pred was on average 7.1 percentage points lower in group 2 than in group 1 (p = 0.03). Mean pinch strength %pred was on average 9.2 percentage points lower in group 2 than in group 1 (p = 0.04). Mean forced vital capacity %pred was on average 4.3 percentage points lower in group 2 than in group 1 (p = 0.01).

Interpretation: In individuals with DMD, DMD mutations predicted to affect Dp140 expression were associated with more severe trajectories of respiratory and upper-limb motor outcomes.

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Conflict of interest statement

Mary Chesshyre, Deborah Ridout, Georgia Stimpson, Silvana De Lucia, and Adnan Manzur report no conflicts of interest.

Erik Niks has been a participant in advisory boards for Edgewise, Italfarmaco, Sarepta Therapeutics, Epirium, Regenxbio, and Janssen. Reimbursements were received by the Leiden University Medical Center. He has also worked as Principal Investigator at the Leiden University Medical Center for clinical trials related to muscular dystrophies from Edgewise, Italfarmaco, Sarepta Therapeutics, Fibrogen, NS Pharma, Reveragen, Santhera, BioMarin, and ML Bio.

Jean‐Yves Hogrel is a coinventor of the MyoGrip, MyoPinch, and MoviPlate devices.

Laurent Servais has received consulting fees from Roche, Biogen, Avexis, Cytokinetics, Sarepta Therapeutics, Biomarin, Pfizer, Santhera, Servier, Biophytis, Audentes, Affinia, BioHaven, Scholar Rock, Dyne, Sysnav, PTC, and Dynacure. He conducts research (newborn screening) funded by Roche, Novartis and Biogen. He is a coinventor of the MoviPlate device.

Volker Straub has served on advisory boards for Astellas Gene Therapies, Biogen, Edgewise Therapeutics, Ipsen, Kate Therapeutics, ML Bio Solutions, Novartis Gene Therapies, PepGen, Roche, Sanofi, Sarepta Therapeutics, Vertex Pharmaceuticals, and Wave Therapeutics. He has received speaking fees or honoraria from Novartis Gene Therapies, Pfizer, Roche, Sanofi, and Sarepta Therapeutics; he has received grants for clinical research from Sarepta Therapeutics and Sanofi.

Valeria Ricotti is cofounder of DiNAQOR, Parterra Limited, Salanar Limited, and Vesalic Limited; in the past, she acted as consultant for Solid Bioscience and Antisense Therapeutics.

Giovanni Baranello is Principal Investigator of clinical trials sponsored by Roche, Novartis, Sarepta Therapeutics, Pfizer, NS Pharma, Reveragen, Percheron, Biomarin, and Scholar Rock; he has received speaker or consulting fees from Sarepta Therapeutics, PTC Therapeutics, Pfizer, Biogen, Novartis Gene Therapies (AveXis), and Roche, and grants from Sarepta Therapeutics, Roche, and Novartis Gene Therapies. UCL has received funding from Sarepta Therapeutics, Roche, Pfizer, Italfarmaco, and Santhera.

Francesco Muntoni reports research funding from Sarepta Therapeutics, and participation in scientific advisory boards or clinical trial monitoring groups for Sarepta Therapeutics, Dyne Therapeutics, Dyne, Pfizer, Italfarmaco, and Santhera.

Figures

**FIGURE 1**
Slopes of yearly progression in grip and pinch strength percentage predicted and MoviPlate score according to the isoform and corticosteroid group. The blue solid line indicates the estimated mean in group 1 for corticosteroid‐exposed participants; the red solid line indicates the estimated mean in group 2 for corticosteroid‐exposed participants; the blue dashed line indicates the estimated mean in group 1 for corticosteroid‐naive participants; the red dashed line indicates the estimated mean in group 2 for corticosteroid‐naive participants; the grey lines indicate individual patient trajectories.

**FIGURE 2**
Slopes of yearly respiratory progression according to isoform group. The blue line indicates the estimated mean in group 1; the red line indicates the estimated mean in group 2; the grey lines indicate the individual patient trajectories. All participants included in the respiratory cohort were corticosteroid‐exposed. Abbreviations: %pred, percentage predicted; FVC, forced vital capacity.

See this image and copyright information in PMC

References

1. Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018. Mar;17(3):251–67. - PMC - PubMed
1. Darras BT, Menache‐Starobinski CC, Hinton V, Kunkel LM. Chapter 30 ‐ Dystrophinopathies. In: Darras BT, Jones HR, Ryan MM, De Vivo Childhood, and Adolescence (Second Edition) DCBTND of I, editors. San Diego: Academic Press; 2015. p. 551–92.
1. Doorenweerd N. Combining genetics, neuropsychology and neuroimaging to improve understanding of brain involvement in Duchenne muscular dystrophy ‐ a narrative review. Neuromuscul Disord. 2020. Jun;30(6):437–42. - PubMed
1. Pane M, Scalise R, Berardinelli A, D'Angelo G, Ricotti V, Alfieri P, et al. Early neurodevelopmental assessment in Duchenne muscular dystrophy. Neuromuscul Disord. 2013. Jun;23(6):451–5. - PubMed
1. Ricotti V, Mandy WPL, Scoto M, Pane M, Deconinck N, Messina S, et al. Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations. Dev Med Child Neurol. 2016. Jan;58(1):77–84. - PubMed

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Dystrophin isoform deficiency and upper-limb and respiratory function in Duchenne muscular dystrophy

Collaborators

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Dystrophin isoform deficiency and upper-limb and respiratory function in Duchenne muscular dystrophy

Authors

Collaborators

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Abstract

Conflict of interest statement

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