Thein S L, Lane D A
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford, England.
Blood. 1988 Nov;72(5):1817-21.
Antithrombin III (ATIII) Northwick Park is caused by a single amino acid substitution, Arg 393---Cys and antithrombin III Glasgow is caused by Arg 393----His. Examination of the genetic code and the sequence of normal antithrombin III revealed that these amino acid substitutions could arise from the substitution of either two nucleotides or a single nucleotide at codon 393 of the antithrombin III gene. In two families, detection of the ATIII variants by genetic linkage analysis was not possible owing to lack of informative RFLP markers. Consequently, we synthesized two 22-base-long oligonucleotides specific for the single-base substitutions in the region of codon 393 and demonstrated by oligonucleotide hybridization that the molecular defect of ATIII Northwick Park is caused by the CGT----TGT mutation at codon 393 and that ATIII Glasgow is caused by the CGT----CAT mutation at codon 393. These oligonucleotide probes should prove useful as an alternative method for early detection of the ATIII variants.
抗凝血酶III（ATIII）诺斯威克帕克型是由单个氨基酸替换，即精氨酸393被半胱氨酸取代引起的，而抗凝血酶III格拉斯哥型是由精氨酸393被组氨酸取代引起的。对正常抗凝血酶III的遗传密码和序列进行检查发现，这些氨基酸替换可能是由于抗凝血酶III基因第393密码子处两个核苷酸或单个核苷酸的替换所致。在两个家族中，由于缺乏信息丰富的限制性片段长度多态性（RFLP）标记，无法通过遗传连锁分析检测到ATIII变体。因此，我们合成了两条针对第393密码子区域单碱基替换的22个碱基长的寡核苷酸，并通过寡核苷酸杂交证明，抗凝血酶III诺斯威克帕克型的分子缺陷是由第393密码子处的CGT→TGT突变引起的，而抗凝血酶III格拉斯哥型是由第393密码子处的CGT→CAT突变引起的。这些寡核苷酸探针应可作为早期检测ATIII变体的一种替代方法。
