Hemophilia A. Detection of molecular defects and of carriers by DNA analysis.
Hemophilia A. Detection of molecular defects and of carriers by DNA analysis.
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血友病 A. 通过 DNA 分析检测分子缺陷和携带者。
DOI：
10.1056/nejm198510033131402
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
J. Toole
中科院分区：
文献类型：
--
作者：
S. Antonarakis;P. Waber;S. Kittur;Achyut S. Patel;H. Kazazian;Marialuisa Mellis;R. Counts;G. Stamatoyannopoulos;E. Bowie;D. Fass;D. Pittman;J. Wozney;J. Toole
为了了解血友病A的分子基础，并通过DNA分析提供杂合子检测和产前诊断，我们使用克隆的因子VIII：C DNA片段研究10个受影响的家庭。在其中四个家庭中，因子VIII：C抑制剂在受影响的人中发展。在一个这样的家庭中，在因子VIII：C基因内约80 kb的缺失被鉴定。通过检测位于缺失终点的异常DNA片段来鉴定缺失的携带者。在另一个家族中，因子VIII：C基因编码区的单核苷酸变化产生无义密码子，导致因子VIII：C合成提前终止。在这个四代家庭的8名女性成员中进行了携带者检测。在第三个家庭的限制性内切酶片段的大小与突变基因的存在相关的一个小的变化，在其他七个家庭的分子缺陷尚未被确定。此外，我们使用了两个常见的多态性位点的因子VIII：C基因区分正常的缺陷基因在四个专性女性运营商的家庭与患者的抑制剂没有发展。在这些家庭的其他成员中可以检测到携带者。这些数据表明，因子VIII：C基因的DNA分析提供了一种准确的方法，携带者检测，并可能在至少50%的血友病A的家系产前诊断。
To understand the molecular basis of hemophilia A and to provide heterozygote detection and prenatal diagnosis by DNA analysis, we used cloned factor VIII:C DNA fragments to study 10 affected families. In four of these families, inhibitors of factor VIII:C had developed in affected persons. In one such family a deletion of approximately 80 kb within the factor VIII:C gene was identified. Carriers of the deletion were identified through detection of an abnormal DNA fragment located at the deletion end points. In another family a single nucleotide change in the coding region of the factor VIII:C gene produced a nonsense codon leading to premature termination of factor VIII:C synthesis. Carrier detection was performed in eight female members of this four-generation family. In a third family a small change in the size of a restriction-endonuclease fragment correlated with the presence of the mutant gene, and in the other seven families the molecular defect has not yet been identified. In addition, we used two common polymorphic sites in the factor VIII:C gene to differentiate the normal from the defective gene in four of six obligate female carriers from families with patients in whom inhibitors did not develop. Carrier detection was possible in other members of these families. These data suggest that DNA analysis of the factor VIII:C gene provides an accurate method of carrier detection and, potentially, of prenatal diagnosis in at least 50 per cent of the pedigrees affected by hemophilia A.
人抗凝血酶 III 的 cDNA 克隆的分离。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Prochownik,EV;Markham,AF;Orkin,SH
通讯作者：
Orkin,SH
利用 DNA 多态性进行产前诊断。
DOI：
10.1056/nejm198305053081803
发表时间：
1983
期刊：
The New England journal of medicine
影响因子：
--
作者：
Boehm,CD;Antonarakis,SE;Phillips3rd,JA;Stetten,G;KazazianJr,HH
通讯作者：
KazazianJr,HH
血红蛋白病的产前诊断--1983。
影响因子：
3.4
作者：
Boehm,CD;KazazianJr,HH
通讯作者：
KazazianJr,HH