Journal Article

Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies

Fanin, Marina, Caumo, Luca, Campadello, Paola, Barp, Andrea, Angelini, Corrado, Pegoraro, Elena, Sorarù, Gianni, Bello, Luca, Semplicini, Claudio, Calore, Chiara

2016

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/4017 / 692/617/375/374 / 82 / Adolescent / Adult / Age Factors / Aged / Base Sequence / Becker's muscular dystrophy / Bone mineral density / Cardiomyopathy, Dilated - complications / Cardiomyopathy, Dilated - diagnosis / Cardiomyopathy, Dilated - genetics / Cardiomyopathy, Dilated - physiopathology / Child / Clinical trials / Clinical Trials as Topic / Duchenne's muscular dystrophy / Dystrophin / Dystrophin - genetics / Dystrophin - metabolism / Dystrophy / Exons / Gene Expression / Humanities and Social Sciences / Humans / Longitudinal Studies / Male / Middle Aged / multidisciplinary / Muscle, Skeletal - metabolism / Muscle, Skeletal - physiopathology / Muscular dystrophy / Muscular Dystrophy, Duchenne - complications / Muscular Dystrophy, Duchenne - diagnosis / Muscular Dystrophy, Duchenne - genetics / Muscular Dystrophy, Duchenne - physiopathology / Mutation / Science / Science (multidisciplinary) / Sequence Deletion / Severity of Illness Index / Skeletal muscle / Walk Test