Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies
Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies
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DOI：
10.1038/srep32439
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发表时间：
2016-09-01
影响因子：
4.6
通讯作者：
Pegoraro, Elena
中科院分区：
文献类型：
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作者：
Bello, Luca;Campadello, Paola;Pegoraro, Elena
我们对贝克肌营养不良（BMD）患者进行了为期1年的六分钟步行测试（6MWT）、北极星动态评估（NSAA）和定时功能测试的纵向研究。免疫印迹法定量测定骨骼肌肌营养不良蛋白。我们将结束于外显子45（“del 45-x”，n = 28）或51（“del x-51”，n = 10）的缺失分组；分离外显子48缺失（“del 48”，n = 10）；和其他突变（n = 21）。只有“del 45-x”组或“其他”组的患者无法走动（n = 5, log-rank p = n.s）或无法跑步（n = 22, p < 0.001）。所有指标均与肌营养不良蛋白的数量呈正相关，与年龄呈负相关，且“del 45-x”组和“其他”组受损程度更严重。1年后NSAA评分显著下降（-0.9 +/- 1.6,p < 0.001）；“del 45-x”组NSAA （-1.3 +/- 1.7, p = 0.001）和6MWT （-12 +/- 31 m, p = 0.059）均下降。我们的结论是，“del x-51”或“del 48”突变的患者有轻度或无症状的BMD，而“del 45-x”突变导致相对严重的虚弱，并在1年内功能恶化。此外，51外显子的跳跃可能比45外显子的跳跃在杜氏肌营养不良症中更有效。
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.