Tachi N, Ohya K, Chiba S, Matsuo M, Patria S Y, Matsumura K
School of Health Sciences, Sapporo Medical University, Japan.
Neurology. 1997 Aug;49(2):579-83. doi: 10.1212/wnl.49.2.579.
Primary deficiency of merosin is the cause of the classic form of congenital muscular dystrophy (CMD) accompanied by brain white matter abnormalities. We report a female infant with dystrophinopathy who was deficient in merosin in skeletal muscle. The patient had a phenotype of typical CMD and white matter abnormalities on brain MRI. Merosin was greatly reduced in the biopsied skeletal muscle. However, the expression of dystroglycan and syntrophin was also greatly reduced, and the immunoreactivity for the antibodies against the cysteine-rich/C-terminal domains of dystrophin was absent in the sarcolemma. Reverse transcriptase polymerase chain reaction analysis of the dystrophin gene revealed a complete lack of exons 71 through 74. In skeletal muscle, only the mutant gene was expressed. These results suggest that the patient is a symptomatic Duchenne muscular dystrophy carrier with skewed X-inactivation. This patient illustrates for the first time that a dystrophin abnormality can cause a secondary deficiency of merosin in dystrophinopathy. The reduction of merosin may account for the clinical phenotype of CMD and correlate with the white matter abnormalities in our patient.
merosin原发性缺乏是伴有脑白质异常的经典型先天性肌营养不良（CMD）的病因。我们报告了一名患有肌营养不良蛋白病且骨骼肌中merosin缺乏的女婴。该患者具有典型CMD的表型且脑MRI显示有白质异常。活检的骨骼肌中merosin显著减少。然而，肌营养不良聚糖和肌营养不良蛋白相关蛋白的表达也显著减少，并且肌膜中不存在针对肌营养不良蛋白富含半胱氨酸/ C末端结构域抗体的免疫反应性。对肌营养不良蛋白基因的逆转录酶聚合酶链反应分析显示外显子71至74完全缺失。在骨骼肌中，仅表达了突变基因。这些结果表明该患者是一名X染色体失活偏向的有症状杜氏肌营养不良携带者。该患者首次表明肌营养不良蛋白异常可导致肌营养不良蛋白病中merosin的继发性缺乏。merosin的减少可能解释了CMD的临床表型并与我们患者的白质异常相关。
