先证者
复合杂合度
凝血酶
外显子
遗传学
分子生物学
化学
基因
生物
等位基因
突变
免疫学
血小板
作者
Eriko Morishita,Makoto Saito,I Kumabashiri,Hitoshi Asakura,Tamotsu Matsuda,Keiichi Yamaguchi
出处
期刊:Blood
[American Society of Hematology]
日期:1992-11-01
卷期号:80 (9): 2275-2280
被引量:21
标识
DOI:10.1182/blood.v80.9.2275.2275
摘要
Abstract A congenitally dysfunctional form of prothrombin, Prothrombin Himi, shows reduced fibrinogen clotting activity, although it retains full hydrolytic activity toward synthetic substrates. To elucidate the structural abnormality of the variant prothrombin, we first performed genetic analysis of dysprothrombin. Polymerase chain reaction amplification of the exons 8 through 14 of the proband and her family members' prothrombin genes, which code the thrombin moiety, followed by single-strand conformation polymorphism analysis, identified two variant conformers in exon 10 specific to this family. One variant allele detected in the father was inherited by the proband and one of her sisters, and the other detected in the mother was also inherited by them. This result indicates that the proband has two different base pair changes in the gene. Sequencing showed two novel point mutations in the proband's gene. One is a T to C transition at position 8751, resulting in the substitution of threonine for methionine at codon 337 (Thrombin Himi I). The other is a G to A transition at 8904, resulting in the substitution of histidine for arginine at codon 388 (Thrombin Himi II). By sequencing analysis of her parents, it was determined that Thrombin Himi I was inherited from the father and Thrombin Himi II from the mother. These results confirm that Prothrombin Himi is compound heterozygous for two dysfunctional prothrombin molecules.
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