Fischer Dirk, Aurino Stefania, Nigro Vincenzo, Schröder Rolf
Muskellabor, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Ann Neurol. 2003 Nov;54(5):674-8. doi: 10.1002/ana.10738.
Mutations in the human alpha-sarcoglycan gene on chromosome 17q21.2 have been shown to cause a severe childhood autosomal recessive muscular dystrophy, a less severe limb girdle muscular dystrophy, exercise intolerance, or asymptomatic hyperCKemia. Here, we describe the clinical findings in a German family harboring a 371 T > C (Ile124Thr) missense mutation in the alpha-sarcoglycan gene. Whereas our index patient, an 11-year-old girl homozygous for this mutation, presented with a severe Duchenne-like phenotype, 7 out of 12 heterozygous mutation carriers from three generations showed mild to moderate scapular winging. In analogy to symptomatic female dystrophinopathy carriers, our results suggest that heterozygous alpha-sarcoglycan gene mutation carriers can be symptomatic with selective muscle weakness. This finding may be attributed to an additional negative variation in a yet unknown modifier gene essential to the function of the sarcoglycan complex in shoulder girdle muscles.
位于17号染色体q21.2区域的人类α-肌聚糖基因发生突变，已被证实会导致严重的儿童常染色体隐性肌肉萎缩症、不太严重的肢带型肌肉萎缩症、运动不耐受或无症状性高肌酸激酶血症。在此，我们描述了一个德国家庭的临床发现，该家庭的α-肌聚糖基因存在371T>C（Ile124Thr）错义突变。我们的索引患者是一名11岁的该突变纯合女孩，表现出严重的杜氏样表型，而来自三代的12名杂合突变携带者中有7人表现出轻度至中度的肩胛翼状胬肉。与有症状的女性肌营养不良蛋白病携带者类似，我们的结果表明，α-肌聚糖基因杂合突变携带者可能会出现选择性肌肉无力的症状。这一发现可能归因于肩胛带肌肉中肌聚糖复合物功能所必需的一个未知修饰基因的额外负向变异。
