Lalić T, Guć-Sćekić M, Djurisić M, Radivojević D, Zamurović D, Todorović S
Srp Arh Celok Lek. 2001 May-Jun;129 Suppl 1:3-5.
About 60% of both Duchenne's muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD) is due to deletions of dystrophin gene. For cases with deletion mutations the "reading frame" hypothesis predicts that deletions which result in disruption of the translation reading frame prevent production of stable protein and are associated with DMD. In contrast, intragenic deletions that involve exons encoding an integral number of triplet codons maintain proper reading frame. The resulting abnormal proteins are stable and partially functional, resulting in a milder and more variable BMD phenotype. To test the validity of this theory,we analyzed 40 patients-19 independent deletions at the DMD/BMD locus. Clinical/molecular correlations based on the altera-tions of the reading frame were valid in 69.2% of cases. After exclusion of: --2 patients with del 3-6 (with no consistent clinical expression); --1 DMD patient with large in-frame deletion; --2 patients that were too young to be classified; --4 patients in whom it was impossible to identify the extent of deletion (del 47 and del 44-45), the correlation between deletion and clinical severity was as predicted in 92.4% of cases. The present data should be useful in establishing the prognosis in individual patients even in sporadic cases with no affected relatives.
杜兴氏肌营养不良症（DMD）和贝克氏肌营养不良症（BMD）约60%的病例是由于肌营养不良蛋白基因缺失所致。对于存在缺失突变的病例，“读码框”假说预测，导致翻译读码框中断的缺失会阻止稳定蛋白质的产生，并与DMD相关。相比之下，涉及编码整数个三联体密码子的外显子的基因内缺失则维持正确的读码框。由此产生的异常蛋白质是稳定的且具有部分功能，导致BMD表型更轻且更具变异性。为了验证该理论的有效性，我们分析了40例患者——DMD/BMD位点的19个独立缺失。基于读码框改变的临床/分子相关性在69.2%的病例中是有效的。排除以下情况后：——2例del 3 - 6患者（无一致的临床表型）；——1例具有大片段框内缺失的DMD患者；——2例年龄太小无法分类的患者；——4例无法确定缺失范围的患者（del 47和del 44 - 45），在92.4%的病例中，缺失与临床严重程度之间的相关性如预期。即使在无患病亲属的散发病例中，目前的数据也应有助于确定个体患者的预后。
