Factor X Frankfurt Imolecular and functional characterization of a hereditary factor X deficiency (Gla+25 to Lys)
作者:
I. Nöbauer-Huhmann,
W. Höller,
B. Krinninger,
P. Turecek,
G. Richter,
I. Scharrer,
E. Forberg,
H. Watzke,
期刊:
Blood Coagulation and Fibrinolysis
(OVID Available online 1998)
卷期:
Volume 9,
issue 2
页码: 143-152
ISSN:0957-5235
年代: 1998
出版商: OVID
关键词: factor X deficiency;molecular characterization;GLA-domain;site directed mutagenesis;mutant;protein function
数据来源: OVID
摘要:
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. Blood Coag Fibrinol 9:143–152 × 1998 Lippincott-Raven Publishers.
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