Prenatal diagnosis and detection of carriers with DNA probes in Duchenne's muscular dystrophy.
Prenatal diagnosis and detection of carriers with DNA probes in Duchenne's muscular dystrophy.
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杜氏肌营养不良症 DNA 探针的产前诊断和携带者检测。
DOI：
10.1056/nejm198704163161604
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Francke,U
中科院分区：
文献类型：
--
作者：
Darras,BT;Harper,JF;Francke,U
我们进行了遗传分析的产前诊断杜氏肌营养不良症和检测的载体状态在五个家庭的七个怀孕的疾病的风险。作为该疾病的遗传标记，我们使用了来自Duchenne肌营养不良症基因座附近或X染色体上基因内的12种不同DNA探针检测的DNA序列多态性。一个男性胎儿的证明携带者母亲被预测为不受影响，这是出生后证实。另一个男性胎儿预计不会受到影响（概率为95%或更高），尽管在被认为是杜兴基因远端的X染色体区域已经确定了交叉事件。不幸的是，出生后血清肌酸激酶水平升高表明婴儿遗传了杜氏突变。三个男性胎儿被预测为66%或95%的概率受到影响而流产，并在胎儿组织中证实了DNA标记等位基因的存在。在一个家庭中，外祖父母是不可用的，最初的遗传解释不得不修改后，第二个男性胎儿进行了基因内探针分析。我们的经验表明，尽管有大量的基因内和侧翼DNA多态性，不确定性往往仍然存在于杜氏肌营养不良症的产前诊断。缺陷是由杜氏突变可能发生的区域的大尺寸提出的。该区域的交叉事件导致两个X染色体之间的DNA交换，可能导致DNA标记研究不准确。此外，常染色体隐性突变可以产生相同的临床表现。（N Engl J Med 1987; 316：985-92.）
We performed genetic analyses for the prenatal diagnosis of Duchenne's muscular dystrophy and detection of the carrier state in five families with seven pregnancies at risk for the disease. As genetic markers for the disorder, we used DNA-sequence polymorphisms detected with 12 different DNA probes derived from the vicinity of the Duchenne's muscular dystrophy locus or from within the gene, on the X chromosome. One male fetus of a proved carrier mother was predicted to be unaffected, and this was confirmed after birth. Another male fetus was predicted to be unaffected (probability, 95 percent or greater), although a crossover event had been identified in a region of the X chromosome thought to be distal to the Duchenne gene. Unfortunately, an elevated serum creatine kinase level after birth indicated that the infant had inherited the Duchenne mutation. Three male fetuses predicted to be affected with 66 percent or 95 percent probabilities were aborted, and the presence of the DNA-marker alleles was confirmed in fetal tissues. In one family, in which the maternal grandparents were unavailable, the initial genetic interpretation had to be revised after a second male fetus was analyzed with intragenic probes. Our experience suggests that despite the large number of intragenic and flanking DNA polymorphisms available, uncertainties often remain in the prenatal diagnosis of Duchenne's muscular dystrophy. Pitfalls are presented by the large size of the region in which Duchenne's mutations can occur. Crossover events in this region, which result in an exchange of DNA between two X chromosomes, can render DNA-marker studies inaccurate. Also, an autosomal recessive mutation can produce the same clinical picture. (N Engl J Med 1987; 316: 985–92.)