Ehrenpreis J, Hillers M, Junkes B, Pfordt M, Schwinger E, Vosberg H P
Max-Planck-Institut für medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, Germany.
Genomics. 1991 Jul;10(3):551-7. doi: 10.1016/0888-7543(91)90435-h.
The most frequent causes for the X-linked muscular dystrophy of the allelic Duchenne (DMD) or Becker (BMD) type are partial deletions of the dystrophin gene. These mutations are accompanied either by disrupted or by preserved translational reading frames in mRNAs derived from the deleted genes. As a rule, the reading frame is destroyed in the more severe DMD, whereas it is preserved in the less severe BMD (M. Koenig et al., 1989, Am. J. Hum. Genet. 45, 498-506). We have analyzed in detail a deletion that was detected in a fetus at risk of DMD. The analysis of this mutation included the delineation of the altered subregion in the dystrophin mRNA. mRNA was isolated from myotubes derived from embryonic DMD myoblasts propagated in vitro. This study was based on enzymatic amplification by the polymerase chain reaction (PCR) of dystrophin mRNA and direct sequencing of the amplified cDNA. Exons 47 to 50 were found to be missing in the mRNA. The splicing of exon 46 to exon 51 resulted in a reading frameshift, indicating that this mutation is likely to be responsible for a DMD type of dystrophy. The clinical diagnosis of DMD for a 10-year-old patient in this family was compatible with the "reading frame" assumption.
等位基因杜兴氏（DMD）或贝克氏（BMD）型X连锁肌营养不良症最常见的病因是肌营养不良蛋白基因的部分缺失。这些突变伴随着来自缺失基因的mRNA中翻译阅读框的破坏或保留。通常，在更严重的DMD中阅读框被破坏，而在较轻的BMD中阅读框被保留（M. 凯尼格等人，1989年，《美国人类遗传学杂志》45卷，498 - 506页）。我们详细分析了在一个有DMD风险的胎儿中检测到的一个缺失。对该突变的分析包括确定肌营养不良蛋白mRNA中改变的亚区域。从体外培养的胚胎DMD成肌细胞衍生的肌管中分离mRNA。本研究基于通过聚合酶链反应（PCR）对肌营养不良蛋白mRNA进行酶促扩增以及对扩增的cDNA进行直接测序。发现mRNA中外显子47至50缺失。外显子46与外显子51的剪接导致阅读框移位，表明该突变可能是导致DMD型肌营养不良症的原因。该家族中一名10岁患者的DMD临床诊断与“阅读框”假设相符。
