A SEVERE MUSCULAR-DYSTROPHY PATIENT WITH AN INTERNALLY DELETED VERY SHORT (110 KD) DYSTROPHIN - PRESENCE OF THE BINDING-SITE FOR DYSTROPHIN-ASSOCIATED GLYCOPROTEIN (DAG) MAY NOT BE ENOUGH FOR PHYSIOLOGICAL-FUNCTION OF DYSTROPHIN
A SEVERE MUSCULAR-DYSTROPHY PATIENT WITH AN INTERNALLY DELETED VERY SHORT (110 KD) DYSTROPHIN - PRESENCE OF THE BINDING-SITE FOR DYSTROPHIN-ASSOCIATED GLYCOPROTEIN (DAG) MAY NOT BE ENOUGH FOR PHYSIOLOGICAL-FUNCTION OF DYSTROPHIN
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DOI：
10.1016/0960-8966(94)00087-p
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发表时间：
1995-09-01
影响因子：
2.8
通讯作者：
ARAHATA, K
中科院分区：
文献类型：
--
作者：
ARIKAWAHIRASAWA, E;KOGA, R;ARAHATA, K
我们报告了一个4岁5个月大的男孩，患有严重的早发性杜氏肌营养不良症的临床特征，他在肌膜处有一个非常短的（110 kDa）营养不良蛋白。该患者的肌营养不良蛋白基因有很大的缺失（外显子2-44），预计会导致阅读框移位。对肌肉中肌营养不良蛋白mRNA的序列分析显示，除了DNA缺失对应的mRNA外，外显子1至51之间还有一个选择性剪接的基因产物，导致阅读框的恢复。肌肉免疫细胞化学分析结果一致；即用抗体对肌膜上的c端、富含半胱氨酸的区域和中央棒状结构域的24个重复单元中的最后3个进行阳性染色，但对识别n端和近端棒状结构域的肌营养不良蛋白的剩余抗体不进行阳性染色。免疫染色保存肌营养不良蛋白相关糖蛋白（dag: 43和50 K）和干酪红蛋白。肌营养蛋白染色呈阳性，但较其他DMD肌肉较淡。这些结果表明，一个极短的肌营养不良蛋白在n端缺乏整个肌动蛋白结合位点，即使该蛋白具有假定的富含dag的半胱氨酸和c端结构域，也不能正常发挥功能，并且仍然具有与肌层膜结合的能力。
We report a 4-yr and 5-month-old boy with severe clinical features of an early-onset Duchenne muscular dystrophy, who had a very short (110 kDa) dystrophin at the sarcolemma. The patient had a large deletion (exons 2-44) of the dystrophin gene which was predicted to cause a reading frame shift. Sequence analysis of dystrophin mRNA in muscle revealed an alternatively spliced gene product from exons 1 to 51 that caused restoration of the reading frame, in addition to an mRNA corresponding to the DNA deletion. A consistent result was obtained by immunocytochemical analysis of muscle; i.e. positive staining for dystrophin at the sarcolemma using antibodies against the C-terminus, cysteine-rich region and last three of 24 repeat units of the central rod-domain, but not for the remaining antibodies for dystrophin that recognize the N-terminal and proximal rod-domains. Immunostaining for dystrophin-associated glycoproteins (DAGs: 43 and 50 K) and merosin were preserved. Utrophin staining was positive but fainter than other DMD muscles. These results suggest that an extremely short dystrophin lacking the entire actin-binding site in the N-terminus cannot function properly even if the protein possesses the putative DAG-binding cysteine-rich and the C-terminal domains, and still has an ability to associate with sarcolemmal membrane.