title: Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies.
abstract: We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ("del 45-x", n = 28) or 51 ("del x-51", n = 10); isolated exon 48 deletion ("del 48", n = 10); and other mutations (n = 21). Only patients in the "del 45-x" or "other" groups became non-ambulatory (n = 5, log-rank p = n.s.) or unable to run (n = 22, p < 0.001). All measures correlated positively with dystrophin quantity and negatively with age, and were significantly more impaired in the "del 45-x" and "other" groups. After one year, NSAA score decreased significantly (-0.9 ± 1.6, p < 0.001); in the "del 45-x" group, both NSAA (-1.3 ± 1.7, p = 0.001) and 6MWT (-12 ± 31 m, p = 0.059) decreased. We conclude that patients with "del x-51" or "del 48" mutations have mild or asymptomatic BMD, while "del 45-x" mutations cause comparatively severe weakness, and functional deterioration in 1 year. Furthermore, exon 51 skipping could be more effective than exon 45 skipping in Duchenne muscular dystrophy.
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Luca
authors: L
authors: Bello
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Paola
authors: P
authors: Campadello
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Andrea
authors: A
authors: Barp
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Marina
authors: M
authors: Fanin
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Claudio
authors: C
authors: Semplicini
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Gianni
authors: G
authors: Sorarù
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Luca
authors: L
authors: Caumo
authors: Department of Cardiac, Thoracic and Vascular Sciences, Cardiology Clinic, University of Padova, Padova, Italy.
authors: Chiara
authors: C
authors: Calore
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Corrado
authors: C
authors: Angelini
authors: Department of Neurosciences, University of Padova, Padova, Italy.
authors: Elena
authors: E
authors: Pegoraro
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D002648:Child; D002986:Clinical Trials as Topic; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D015870:Gene Expression; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D017384:Sequence Deletion; D012720:Severity of Illness Index; D000070857:Walk Test
chemical_list: D016189:Dystrophin