A CDNA CLONE FROM THE DUCHENNE BECKER MUSCULAR-DYSTROPHY GENE
A CDNA CLONE FROM THE DUCHENNE BECKER MUSCULAR-DYSTROPHY GENE
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DOI：
10.1038/328434a0
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发表时间：
1987-07-30
期刊：
影响因子：
64.8
通讯作者：
RAY, PN
中科院分区：
文献类型：
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作者：
BURGHES, AHM;LOGAN, C;RAY, PN
Duchenne肌营养不良症(DMD)是最常见的肌营养不良症，每3,000名活产男婴中就有1名受到影响(见参考文献1，2)。DMD和轻度的Becker肌营养不良症(BMD)都是X连锁的。有许多女性患者都具有X常染色体易位，X染色体上的交换点总是发生在染色体Xp21带内。这与连锁和缺失数据一起，将该基因定位在Xp21带(参考文献5-7)。这一区域的DNA片段是用一名Xp21大缺失患者和一名t(X：21)易位患者克隆的。前者(PERT87)含有DXS164基因座，后者(XJ)含有DXS206基因座。来自这两个区域的亚克隆可以检测到11%的DMD患者8-12的∼缺失。一个与DXS164基因外显子相对应的胎儿肌肉互补基因克隆已经被分离出来，并检测到16kb的转录。我们从DXS206基因座分离了一个成人肌肉的cDNA克隆，该克隆在成人肌肉中检测到一个16kb的mRNA。该克隆含有位于DXS206、DXS164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105kb或更大的大内含子内，表明易位破坏了DMD/BMD基因，导致了该患者的疾病。
Duchenne muscular dystrophy (DMD) is the most common of the muscular dystrophies affecting one in 3,000 live male births (see refs 1, 2 for review). 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 (refs 3, 4). This, together with linkage and deletion data, has localized the gene at band Xp21 (refs 5–7). DNA fragments from this region have been cloned using a patient with a large Xp21 deletion8and from a patient with a t(X:21) translocation9. The former clones (pERT87) comprise the DXS164 locus and the latter clones (XJ) the DXS206 locus. Subclones from both regions allow the detection of deletions in ∼11% of DMD patients8–12. A fetal muscle complementary DNA clone corresponding to exons in the DXS164 locus has been isolated and detects a 16-kilobase (kb) transcript13. 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.