| Autor: |
I M, Nöbauer-Huhmann, W, Höller, B, Krinninger, P L, Turecek, G, Richter, I, Scharrer, E, Forberg, H H, Watzke |
| Rok vydání: |
1998 |
| Předmět: |
|
| Zdroj: |
Blood coagulationfibrinolysis : an international journal in haemostasis and thrombosis. 9(2) |
| ISSN: |
0957-5235 |
| Popis: |
A family with hereditary factor X deficiency is presented. One member, a 25-year-old man, showed a mild bleeding tendency. His factor X activity (extrinsic: 56%; intrinsic: 55%; Russell's viper venom: 57%) and his level of circulating factor X antigen (55% of normal) were markedly reduced. Analysis of his factor X gene revealed a single point mutation within exon II resulting in the substitution of +25 Gla (GAA) by Lys (AAA). The mutation was determined by gene analysis to be heterozygous in this patient, his mother and one of his brothers. Clotting assays of factor X purified from the plasma of the index patient revealed an activity of 89% of normal upon activation with Russell's viper venom, 77% of normal in the intrinsic and 81% of normal in the extrinsic coagulation pathway. The mutation responsible for the substitution of Lys for Gla+25 was introduced into an expression plasmid containing a wild type factor X cDNA and expressed in a mammalian cell line. Factor X antigen levels in the cell lysates and in the supernatant were identical in the mutant and wild type constructs. The specific activity of the factor X expressed from the mutant construct was 3% compared with the wild type construct. These data demonstrate that the substitution of Lys for Gla+25 results not only in a reduced level of factor X in the affected family members, but also in a substantial loss of specific factor X activity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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