Burghes A H, Logan C, Hu X, Belfall B, Worton R G, Ray P N
Nature. 1987;328(6129):434-7. doi: 10.1038/328434a0.
Duchenne muscular dystrophy (DMD) is the most common of the muscular dystrophies affecting one in 3,000 live male births. Both DMD and the mild form, Becker muscular dystrophy (BMD), are X-linked. There are a number of females affected by the disease who all possess an X-autosome translocation, with the exchange point in the X always occurring within chromosome band Xp21. This, together with linkage and deletion data, has localized the gene at band Xp21. DNA fragments from this region have been cloned using a patient with a large Xp21 deletion and from a patient with a t(X:21) translocation. The former clones (pERT 87) comprise the DXS164 locus and the latter clones (XJ) the DXS206 locus. Subclones from both regions allow the detection of deletions in approximately 11% of DMD patients. A fetal muscle complementary DNA clone corresponding to exons in the DXS164 locus has been isolated and detects a 16-kilobase (kb) transcript. We present the isolation of an adult muscle cDNA clone from the DXS206 locus that detects a 16-kb mRNA in adult human muscle. The cDNA clone contains exons that map in the DXS206 locus, the DXS164 locus, and on the centromeric side of these cloned regions. The t(X;21) translocation exchange points occurs within a large intron of 105 kb or larger, indicating that the translocation has disrupted the DMD/BMD gene to cause the disease in this patient.
杜氏肌营养不良症(DMD)是最常见的肌营养不良症,在每3000例活产男婴中就有1例受影响。DMD和症状较轻的贝克肌营养不良症(BMD)均为X连锁遗传。有许多女性受此病影响,她们都拥有X-常染色体易位,X染色体上的交换点总是出现在染色体带Xp21内。这一点,连同连锁和缺失数据,已将该基因定位在Xp21带。已使用一名患有大的Xp21缺失的患者以及一名患有t(X:21)易位的患者克隆了该区域的DNA片段。前者的克隆(pERT 87)包含DXS164位点,后者的克隆(XJ)包含DXS206位点。来自这两个区域的亚克隆能够检测出约11%的DMD患者中的缺失情况。已分离出一个与DXS164位点外显子相对应的胎儿肌肉互补DNA克隆,并检测到一个16千碱基(kb)的转录本。我们展示了从DXS206位点分离出的一个成人肌肉cDNA克隆,该克隆在成人人类肌肉中检测到一个16-kb的mRNA。该cDNA克隆包含定位在DXS206位点、DXS164位点以及这些克隆区域着丝粒一侧的外显子。t(X;21)易位交换点出现在一个105 kb或更大的大内含子内,这表明该易位破坏了DMD/BMD基因,从而导致该患者患病。