Antithrombin III tours gene: identification of a point mutation leading to an arginine----cysteine replacement in a silent deficiency.
Antithrombin III tours gene: identification of a point mutation leading to an arginine----cysteine replacement in a silent deficiency.
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抗凝血酶 III 旅游基因：鉴定出导致静默缺陷中精氨酸----半胱氨酸替代的点突变。
DOI：
10.1093/nar/14.5.2408
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发表时间：
1986
影响因子：
14.9
通讯作者：
M. Zakin
中科院分区：
文献类型：
--
作者：
N. Duchange;J. Chasse;G. Cohen;M. Zakin
先天性抗凝血酶III(AT III)缺乏与血栓性疾病的高发生率有关。然而，已经报道了几个与影响AT III肝素结合位点的质量缺陷相对应的无症状家族性病例。AT III Tours是在一个杂合状态的法国家庭的9个成员(Chasse，JF，Esnard，F.，Guitton，JD，Mouray，H.，Perigois，F.，Fauconneau，G.和Gauthier，F.(1984)Thromb)中发现的这种沉默缺陷。结果34,297-302)。我们从一个个体的白细胞DNA中制备了基因组文库，并与我们先前分离的AT III基因进行杂交(Huynh-Dinh，T.，Duchange，N.，Zakin，MM，Lemarchand，A.和IGolen，J.(1985)Proc.娜塔莉。阿卡德。SCI。美国82,7510-7514)。利用AT III编码序列(Prochownik，EV，Markham，AF和Orkin，SH(1983)J.Biol)中自然产生的PstI多态来区分正常和突变的等位基因。化学。258,8389-8394)。核苷酸序列使我们能够在外显子2中识别一个单核苷酸变异C-+T，导致蛋白质第47位的精氨酸-半胱氨酸替换。同样的氨基酸变化以前在AT III富山先天性缺陷(Koide，T.，Odani，S.，Takahashi，K.，Ono，T.和Sakuragawa，N.(1984)Proc)的蛋白质水平上被描述过。娜塔莉。阿卡德。SCI。美国81,289-293)。
Congenital antithrombin III (AT III) deficiencies are associated with high incidence of thrombotic disorders. However, several silent familial cases have been reported and correspond to qualitative defects affecting the heparin binding site of AT III. AT III Tours is such a silent deficiency detected in nine members of a French family at the heterozygous state (Chasse, JF, Esnard, F., Guitton, JD, Mouray, H., Perigois, F., Fauconneau, G. and Gauthier, F.(1984) Thromb. Res. 34, 297-302).We prepared a genomic library from the leucocyte DNA of one individual and isolated the AT III Tours gene by hybridization with the AT III cDNA we isolated previously (Huynh-Dinh, T., Duchange, N., Zakin, MM, Lemarchand, A. and Igolen, J.(1985) Proc. Natl. Acad. Sci. USA 82, 7510-7514). The normal and mutant alleles were differentiated by using a naturally occurring PstI polymorphis within the AT III coding sequence (Prochownik, EV, Markham, AF and Orkin, SH (1983) J. Biol. Chem. 258, 8389-8394) after a family study with this restriction enzyme. Nucleotide sequence allowed us to identify in exon 2 a single nucleotide variation C-+ T leading to an arginine--cysteine replacement at position 47 inthe protein. The same amino acid change was previously described at theprotein level in AT III Toyama congenital deficiency (Koide, T., Odani, S., Takahashi, K., Ono, T. and Sakuragawa, N.(1984) Proc. Natl. Acad. Sci. USA 81,289-293).