Very Low Residual Dystrophin Quantity Is Associated with Milder Dystrophinopathy

• Published in: Annals of neurology 2021-02, Vol.89 (2), p.280-292
• Main Authors: Feraudy, Yvan, Ben Yaou, Rabah, Wahbi, Karim, Stalens, Caroline, Stantzou, Amalia, Laugel, Vincent, Desguerre, Isabelle, Servais, Laurent, Leturcq, France, Amthor, Helge
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenal Cortex Hormones - therapeutic use; Adult; Age of Onset; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Becker's muscular dystrophy; Biopsy; Blotting, Western; Child; Clinical outcomes; Cohort Studies; Disease Progression; Duchenne's muscular dystrophy; Dystrophin; Dystrophin - genetics; Dystrophin - metabolism; Dystrophy; Heart; Human health sciences; Humans; Life Sciences; Male; Mobility Limitation; Mortality; Muscle, Skeletal - metabolism; Muscles; Muscular dystrophy; Muscular Dystrophy, Duchenne - metabolism; Muscular Dystrophy, Duchenne - physiopathology; Muscular Dystrophy, Duchenne - therapy; Mutation; Neurobiology; Neurologie; Neurology; Neurons and Cognition; Noninvasive Ventilation - statistics & numerical data; Ostomy; Oxadiazoles - therapeutic use; Pediatrics; Phenotype; Phenotypes; Proportional Hazards Models; Proteins; Pédiatrie; Retrospective Studies; Sciences de la santé humaine; Severity of Illness Index; Signs and symptoms; Spinal Fusion - statistics & numerical data; Stroke Volume; Tracheostomy; Tracheostomy - statistics & numerical data; Ventilation; Ventricle; Vital Capacity; Young Adult
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.25951

Objective This study was undertaken to determine whether a low residual quantity of dystrophin protein is associated with delayed clinical milestones in patients with DMD mutations. Methods We performed a retrospective multicentric cohort study by using molecular and clinical data from patients with DMD mutations registered in the Universal Mutation Database–DMD France database. Patients with intronic, splice site, or nonsense DMD mutations, with available muscle biopsy Western blot data, were included irrespective of whether they presented with severe Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD). Patients were separated into 3 groups based on dystrophin protein levels. Clinical outcomes were ages at appearance of first symptoms; loss of ambulation; fall in vital capacity and left ventricular ejection fraction; interventions such as spinal fusion, tracheostomy, and noninvasive ventilation; and death. Results Of 3,880 patients with DMD mutations, 90 with mutations of interest were included. Forty‐two patients expressed no dystrophin (group A), and 31 of 42 (74%) developed DMD. Thirty‐four patients had dystrophin quantities