Hoffman E P, Fischbeck K H, Brown R H, Johnson M, Medori R, Loike J D, Harris J B, Waterston R, Brooke M, Specht L
Division of Genetics, Children's Hospital, Boston, MA.
N Engl J Med. 1988 May 26;318(21):1363-8. doi: 10.1056/NEJM198805263182104.
A deficiency of the protein dystrophin has recently been shown to be the probable cause of Duchenne's muscular dystrophy. We sought to determine the relation between the clinical phenotype and the status of dystrophin in muscle-biopsy specimens from 103 patients with various neuromuscular disorders. We found very low levels (less than 3 percent of normal levels) or no dystrophin in the severe Duchenne phenotype (35 of 38 patients), low concentrations of dystrophin in the intermediate (outlier) phenotype (4 of 7), and dystrophin of abnormal molecular weight in the mild Becker phenotype (12 of 18). Normal levels of dystrophin of normal molecular weight were found in nearly all the patients (38 of 40) with 20 other neuromuscular disorders we studied. These data show the clinical consequences of both quantitative alterations (in Duchenne's and intermediate dystrophy) in a single protein. The biochemical assay for dystrophin should prove helpful in delineating myopathies that overlap clinically with Duchenne's and Becker's dystrophies, and it shows promise as an accurate diagnostic tool.
最近研究表明,蛋白质抗肌萎缩蛋白的缺乏可能是杜兴氏肌营养不良症的病因。我们试图确定103例患有各种神经肌肉疾病患者的肌肉活检标本中临床表型与抗肌萎缩蛋白状态之间的关系。我们发现,严重杜兴氏表型(38例患者中的35例)中抗肌萎缩蛋白水平极低(低于正常水平的3%)或完全没有,中间型(异常型)表型(7例中的4例)中抗肌萎缩蛋白浓度较低,轻度贝克型表型(18例中的12例)中抗肌萎缩蛋白分子量异常。在我们研究的另外20种神经肌肉疾病的几乎所有患者(40例中的38例)中,发现了分子量正常的抗肌萎缩蛋白正常水平。这些数据显示了单一蛋白质定量改变(在杜兴氏和中间型肌营养不良症中)的临床后果。抗肌萎缩蛋白的生化检测在区分临床上与杜兴氏和贝克氏肌营养不良症重叠的肌病方面应会有所帮助,并且它有望成为一种准确的诊断工具。