CHARACTERIZATION OF TRANSLATIONAL FRAME EXCEPTION PATIENTS IN DUCHENNE BECKER MUSCULAR-DYSTROPHY
CHARACTERIZATION OF TRANSLATIONAL FRAME EXCEPTION PATIENTS IN DUCHENNE BECKER MUSCULAR-DYSTROPHY
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DOI：
10.1093/hmg/2.6.737
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发表时间：
1993-06-01
影响因子：
3.5
通讯作者：
BURGHES, AHM
中科院分区：
文献类型：
--
作者：
WINNARD, AV;KLEIN, CJ;BURGHES, AHM
有缺失的Duchenne肌营养不良症(DMD)患者的临床进展可以通过缺失维持还是破坏翻译阅读框架(移码假说)在93%的病例中预测。我们已经确定并研究了一些患者，他们的缺失不符合翻译框架假说。移码假说最常见的例外是外显子3至7的缺失，这会扰乱翻译阅读框架。我们确定了一名Becker肌营养不良症(BMD)患者、一名中间人和一名DMD患者存在该缺失。在这三个病例中，Dystrophin均被检测到并定位于细胞膜。1例外显子4-18缺失的DMD患者未产生抗肌营养不良蛋白。1例轻度中间表型，外显子45缺失，导致阅读框改变，未产生抗肌营养不良蛋白。两名有较大下层酶缺失的患者具有不一致的表型(外显子3-41，DMD；外显子13-48，BMD)，但都产生了定位于肌膜的抗肌营养不良蛋白。DMD患者，113，表明Duchenne患者可以产生与某些Beckers相当的水平的具有完整羧基末端的抗肌营养不良蛋白。来自这些患者的dystrophin分析，以及文献中报道的患者，表明不止一个结构域可以将dystrophin定位到肌膜。最后，数据显示，尽管大多数患者表现出临床严重程度与分子数据的相关性，但也有少数患者不符合。
The clinical progression of Duchenne muscular dystrophy (DMD) patients with deletions can be predicted in 93% of cases by whether the deletion maintains or disrupts the translational reading frame (frameshift hypothesis). We have identified and studied a number of patients who have deletions that do not conform to the translational frame hypothesis. The most common exception to the frameshift hypothesis is the deletion of exons 3 to 7 which disrupts the translational reading frame. We identified a Becker muscular dystrophy (BMD) patient, an intermediate, and a DMD patient with this deletion. In all three cases, dystrophin was detected and localized to the membrane. One DMD patient with an inframe deletion of exons 4-18 produced no dystrophin. One patient with a mild intermediate phenotype and a deletion of exon 45, which shifts the reading frame, produced no dystrophin. Two patients with large inframe deletions had discordant phenotypes (exons 3-41, DMD; exons 13-48, BMD), but both produced dystrophin that localized to the sarcolemma. The DMD patient, 113, indicates that dystrophin with an intact carboxy terminus can be produced in Duchenne patients at levels equivalent to some Beckers. The dystrophin analysis from these patients, together with patients reported in the literature, indicate that more than one domain can localize dystrophin to the sarcolemma. Lastely, the data shows that although most patients show correlation of clinical severity to molecular data, there are rare patients which do not conform.