Gangopadhyay S B, Sherratt T G, Heckmatt J Z, Dubowitz V, Miller G, Shokeir M, Ray P N, Strong P N, Worton R G
Genetics Department, Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Hum Genet. 1992 Sep;51(3):562-70.
In a previous study we identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. We have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases we detected slightly lower-molecular-weight dystrophin in 12%-15% abudance relative to the normal. By sequencing amplified mRNA we have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternative splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame.
在之前的一项研究中，我们鉴定出14例患有杜氏肌营养不良症（DMD）或其较轻变体贝克肌营养不良症（BMD）的病例，这些病例存在外显子3 - 7的缺失，这种缺失预计会改变mRNA的翻译阅读框并导致严重的表型。我们检查了7例具有轻度或中度表型的肌肉活检样本中的抗肌萎缩蛋白及其mRNA。在所有病例中，我们检测到相对于正常情况，抗肌萎缩蛋白的分子量略低，丰度为12% - 15%。通过对扩增的mRNA进行测序，我们发现外显子2与外显子8拼接，这种拼接产生了移码的mRNA，并且没有发现可能参与轻度表型患者抗肌萎缩蛋白mRNA阅读框恢复的可变剪接的证据。有人提出其他转录和转录后机制，如隐蔽启动子、核糖体移码和重新起始，可能在恢复阅读框中发挥一定作用。
