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

Journal article

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.

Authors: Chesshyre, M; Ridout, D; Stimpson, G; Ricotti, V; De Lucia, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Developmental Medicine & Child Neurology
• Publication date: 2025-03-14
• Acceptance date: 2025-01-24
• DOI: 10.1111/dmcn.16282
• EISSN: 1469-8749
• ISSN: 0012-1622
• Language: English