Deletion of exon 26 of the dystrophin gene is associated with a mild Becker muscular dystrophy phenotype
Deletion of exon 26 of the dystrophin gene is associated with a mild Becker muscular dystrophy phenotype
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发表时间：
2011-12
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通讯作者：
N. Witting;M. Duno;J. Vissing
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作者：
N. Witting;M. Duno;J. Vissing
随着外显子跳跃疗法在杜氏肌营养不良症中的应用，了解肌营养不良蛋白基因的每个外显子对蛋白质表达以及表型的作用变得越来越重要。在本报告中，我们介绍了两名相关男性，其 BMD 异常轻微，且与外显子 26 缺失相关。先证者是一名 23 岁男性，运动里程碑略有延迟，行走年龄为 1.5 岁。他没有抱怨肌肉无力，但有肌肉疼痛。临床检查显示没有肌肉萎缩或力量丧失，但他的 CK 为 1500-7000 U/l。肌肉活检显示营养不良的变化。他患有肌张力障碍、轻度智力障碍、身材矮小和神经病等合并症。先证者母亲的兄弟在43岁时前来就医。他抱怨肌肉疼痛。检查时发现 MRC 4+ 级髋关节伸展麻痹和离散的小腿肥大。肌酸激酶正常或最大升高至 500U/l。肌肉活检呈肌病性，纤维尺寸变化增加，内部细胞核较多，但无营养不良。未发现合并症。在这两种情况下，蛋白质印迹均显示肌营养不良蛋白条带减少。遗传评估显示，两者的肌营养不良蛋白基因的外显子 26 均被删除。这是首次描述抗肌营养不良蛋白基因外显子 26 缺失的患者。假设先证者的合并症不相关，外显子 26 缺失会导致非常轻微的表型。这可能对规划杜氏肌营养不良症的外显子跳跃疗法感兴趣。该报告还显示 BMD 可能与正常 CK 一起出现。
With the possible introduction of exon skipping therapy in Duchenne muscular dystrophy, it has become increasingly important to know the role of each exon of the dystrophin gene to protein expression, and thus the phenotype. In this report, we present two related men with an unusually mild BMD associated with an exon 26 deletion. The proband, a 23-year-old man, had slightly delayed motor milestones, walking 1½ years old. He had no complaints of muscle weakness, but had muscle pain. Clinical examination revealed no muscle wasting or loss of power, but his CK was 1500-7000 U/l. Muscle biopsy showed dystrophic changes. He had comorbidity with dystonia, slight mental retardation, low stature and neuropathy. The brother of the proband's mother came to medical attention when he was 43 years old. He complained about muscle pain. On examination, a MRC grade 4+ hip extention palsy and a discrete calf hypertrophy was noted. Creatine kinase was normal or raised maximally to 500U/l. The muscle biopsy was myopathic with increased fiber size variation and many internal nuclei, but no dystrophy. No comorbidity was found. In both cases, western blot showed a reduced dystrophin band. Genetic evaluation revealed a deletion of exon 26 of the dystrophin gene in both. This is the first description of patients with a exon 26 deletion of the dystrophin gene. Assuming the proband's comorbidity is unrelated, exon 26 deletion results in a very mild phenotype. This might be of interest in planning exon skipping therapy for Duchenne muscular dystrophy. This report also shows that BMD may present with a normal CK.