Phenotypic homozygous activated protein C resistance associated with compound heterozygosity for Arg506Gln (factor V leiden) and His1299Arg substitutions in factor V

被引:50
作者
Castaman, G
Lunghi, B
Missiaglia, E
Bernardi, F
Rodeghiero, F
机构
[1] SAN BORTOLO HOSP,HAEMOPHILIA & THROMBOSIS CTR,I-36100 VICENZA,ITALY
[2] UNIV FERRARA,DEPT BIOCHEM & MOL BIOL,I-44100 FERRARA,ITALY
关键词
inherited thrombophilia; factor V; FV Leiden; APC resistance;
D O I
10.1046/j.1365-2141.1997.3993213.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Two patients from two unrelated families with a history of thrombosis showed severe plasma activated protein C (APC) resistance. However, genotypic analysis demonstrated that the patients were heterozygous for factor V (FV) Leiden mutation. Coagulation studies revealed that FV clotting activity and antigen were similarly reduced at about 50% of normal in the patients. One brother of propositus A also showed the same abnormalities. Genetic analysis showed that, in addition to FV Leiden mutation in exon 10 of the FV gene (G1691A), these patients had a transition in exon 13 of the FV gene (A4070G; R2 allele) predicting His1299Arg substitution in the mature FV. Study by RT-PCR of platelet FV mRNA indicated that the mRNA produced by the FV gene, marked by the R2 allele, was reduced in amount in both pseudohomozygous patients of family A. The R2 allele has previously been demonstrated to be significantly associated with plasma FV deficiency in the Italian population. The presence of FV deficiency did not protect the propositi from thrombosis. These data confirm that genotypic analysis is mandatory in patients with phenotypic severe APC resistance before these patients are definitely classified as homozygotes for FV Leiden and that further genotypic analysis is advisable.
引用
收藏
页码:257 / 261
页数:5
相关论文
共 14 条
[1]   MUTATION IN BLOOD-COAGULATION FACTOR-V ASSOCIATED WITH RESISTANCE TO ACTIVATED PROTEIN-C [J].
BERTINA, RM ;
KOELEMAN, BPC ;
KOSTER, T ;
ROSENDAAL, FR ;
DIRVEN, RJ ;
DERONDE, H ;
VANDERVELDEN, PA ;
REITSMA, PH .
NATURE, 1994, 369 (6475) :64-67
[2]  
BERTINA RM, 1995, THROMB HAEMOSTASIS, V74, P449
[3]  
DERONDE H, 1994, THROMB HAEMOSTASIS, V72, P880
[4]  
GREENGARD JS, 1995, THROMB HAEMOSTASIS, V73, P1361
[5]   COMPLETE CDNA AND DERIVED AMINO-ACID-SEQUENCE OF HUMAN FACTOR-V [J].
JENNY, RJ ;
PITTMAN, DD ;
TOOLE, JJ ;
KRIZ, RW ;
ALDAPE, RA ;
HEWICK, RM ;
KAUFMAN, RJ ;
MANN, KG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (14) :4846-4850
[6]  
Lunghi B, 1996, THROMB HAEMOSTASIS, V75, P45
[7]   WORLD DISTRIBUTION OF FACTOR-V LEIDEN [J].
REES, DC ;
COX, M ;
CLEGG, JB .
LANCET, 1995, 346 (8983) :1133-1134
[8]  
Rodeghiero F, 1996, THROMB HAEMOSTASIS, V76, P226
[9]   HIGH-RISK OF THROMBOSIS IN PATIENTS HOMOZYGOUS FOR FACTOR-V LEIDEN (ACTIVATED PROTEIN-C RESISTANCE) [J].
ROSENDAAL, FR ;
KOSTER, T ;
VANDENBROUCKE, JP ;
REITSMA, PH .
BLOOD, 1995, 85 (06) :1504-1508
[10]  
SACCHI E, 1995, THROMB HAEMOSTASIS, V73, P746