Speer A, Spiegler A W, Hanke R, Grade K, Giertler U, Schieck J, Forrest S, Davies K E, Neumann R, Bollmann R
Department of Human Molecular Genetics, Academy of Science GDR, Berlin.
J Med Genet. 1989 Jan;26(1):1-5. doi: 10.1136/jmg.26.1.1.
Two cDNA probes, cf23a and cf56a, identify deletions of selected exons in about 50% of our DMD/BMD patients. We have estimated the most likely order of the 11 exons detectable with both probes with respect to the different extensions of the deletions. In one of our BMD pedigrees, the observed deletion could be traced in the affected males through three generations. This result shows that with the use of cDNA probes detecting deletions, the only risk of error in genomic prenatal diagnosis is the general high frequency of new mutations for DMD/BMD. This is important progress in diagnosis compared to the 2 to 5% risk of misdiagnosis because of crossing over events using conventional linkage analysis with bridging or intragenic probes. The first prenatal diagnosis of an unaffected fetus of a woman who is a DMD carrier according to ultrasound examination is described. In one of our DMD males, the cDNA probe cf56a detects a deletion breakpoint. His sister also shows the altered band and is therefore a DMD carrier, while his mother has a totally normal band pattern. The interpretation of this observation could be either germline mosaicism or two identical new mutations. The identification of deletion breakpoints is a new diagnostic strategy, especially for carrier determination, which excludes misdiagnosis owing to crossing over events and the problems of dosage estimation. It is, however, limited by the low frequency of breakpoints detectable with cDNA probes. Therefore, the generation of new intron probes in this region is an important goal.
两种cDNA探针cf23a和cf56a，在约50%的杜氏肌营养不良症（DMD）/贝克型肌营养不良症（BMD）患者中可识别特定外显子的缺失。我们已根据缺失的不同范围估算了两种探针均可检测到的11个外显子的最可能顺序。在我们的一个BMD家系中，观察到的缺失可在三代受影响男性中追踪到。这一结果表明，使用检测缺失的cDNA探针，基因组产前诊断中唯一的错误风险是DMD/BMD新突变的总体高频率。与使用桥接或基因内探针进行传统连锁分析因交叉事件导致2%至5%的误诊风险相比，这是诊断方面的重要进展。本文描述了首例根据超声检查对一名DMD携带者女性的未受影响胎儿进行的产前诊断。在我们的一名DMD男性患者中，cDNA探针cf56a检测到一个缺失断点。他的妹妹也显示出改变的条带，因此是一名DMD携带者，而他的母亲条带模式完全正常。对这一观察结果的解释可能是生殖系嵌合体或两个相同的新突变。缺失断点的识别是一种新的诊断策略，尤其对于携带者的确定，它排除了因交叉事件导致的误诊以及剂量估计问题。然而，它受到cDNA探针可检测到的断点频率较低的限制。因此，在该区域生成新的内含子探针是一个重要目标。
