Characterization of five partial deletions of the factor VIII gene.
Characterization of five partial deletions of the factor VIII gene.
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因子 VIII 基因五次部分缺失的表征。
DOI：
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发表时间：
1987
影响因子：
11.1
通讯作者：
H. Kazazian
中科院分区：
文献类型：
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作者：
H. Youssoufian;S. Antonarakis;S. Aronis;G. Tsiftis;D. Phillips;H. Kazazian
血友病A是一种X-连锁的凝血障碍，由因子VIII缺乏引起。通过使用克隆的DNA探针，我们已经表征了来自一组83名血友病A患者的以下5种不同的因子VIII基因部分缺失：（i）7-磷酸酶（kb）缺失，其消除了外显子6;（ii）2.5-kb缺失，其消除了外显子14的5'序列;（iii）至少7 kb缺失，其消除了外显子24和25;（iv）消除外显子23-25的至少16 kb的缺失;和前四个缺失与重度血友病A相关。相比之下，最后一个缺失与中度疾病相关，可能是因为中度疾病的框内剪接，可能是因为相邻外显子的框内剪接。这些部分基因缺失的患者中没有一个有凝血因子VIII的循环抑制剂。一个缺失发生在外祖母的生殖细胞中，而第二个缺失发生在外祖父的生殖细胞中。这些观察结果表明，从头缺失的X-连锁基因可以发生在男性或女性配子。
Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, we have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes.