Mutations in coagulation factor XIII subunit A in severe factor XIII deficiency patients: five novel mutations detected

Haemophilia ◽  
2011 ◽  
pp. no-no
Author(s):  
S. SHANBHAG ◽  
S. SHETTY ◽  
K. GHOSH
Keyword(s):  
Factor Xiii ◽  
Coagulation Factor ◽  
Novel Mutations ◽  
Factor Xiii Deficiency ◽  
Subunit A ◽  
Coagulation Factor Xiii

Spontaneous regression of the inhibitor against the coagulation factor XIII A subunit in acquired factor XIII deficiency

2010 ◽  
Vol 104 (12) ◽  
pp. 1284-1285 ◽  
Author(s):  
Kentaro Okubo ◽  
Toshiro Ito ◽  
Nobuo Okumura ◽  
Masayoshi Souri ◽  
Akitada Ichinose ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Spontaneous Regression ◽  
Coagulation Factor ◽  
Factor Xiii Deficiency ◽  
Coagulation Factor Xiii ◽  
A Subunit

A Point Mutation in an Invariant Splice Acceptor Site Results in a Decreased mRNA Level in a Patient with Severe Coagulation Factor XIII Subunit A Deficiency

1995 ◽  
Vol 74 (02) ◽  
pp. 584-589 ◽  
Author(s):  
Peter Vreken ◽  
René W L M Niessen ◽  
Marjolein Peters ◽  
Marianne C L Schaap ◽  
Johanna G M Zuithoff-Rijntjes ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Mrna Level ◽  
Coagulation Factor ◽  
Splice Acceptor Site ◽  
Mononuclear Leukocytes ◽  
Acceptor Site ◽  
Mrna Levels ◽  
Splice Acceptor ◽  
Subunit A ◽  
Coagulation Factor Xiii

SummaryAmplification and sequencing of exons I-XV of the gene encoding subunit A of coagulation factor XIII (FXIII) in a patient with severe subunit A deficiency revealed a single G → A base substitution at the last position of intron E, mutating the invariant AG dinucleotide splice acceptor site to AA. Northern blot analysis of FXIII subunit A mRNA levels in peripheral mononuclear leukocytes showed that this mutation leads to an undetectable FXIII subunit A mRNA level, suggesting that the mutant transcript is either highly unstable or only spliced at low efficiency. Despite this low mRNA level we were able to amplify cDNA fragments containing the exonV-exonVI junction. Sequence analysis showed that the AA dinucleotide is not recognized by the splicing machinery. Instead, an AG dinucleotide located seven bases downstream of the mutated splice acceptor site is used as alternative acceptor. The resulting, alternatively spliced, FXIII subunit A transcript contains a deletion of the first seven bases of exon VI, while translation continues out of frame and leads to a premature stop codon 27 bases thereafter.

scholarly journals Pathogenicity analysis of variations and prenatal diagnosis in a hereditary coagulation factor XIII deficiency family

Hematology ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 501-509 ◽  
Author(s):  
Liwei Sun ◽  
Qijiang Yan ◽  
Yonghua Wang ◽  
Hualei Luo ◽  
Peng Du ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Factor Xiii Deficiency ◽  
Coagulation Factor Xiii

Effect of Val34Leu Polymorphism on the Activation of the Coagulation Factor XIII-A

2000 ◽  
Vol 84 (10) ◽  
pp. 595-600 ◽  
Author(s):  
H. Mikkola ◽  
G. Szôke ◽  
G. Haramura ◽  
L. Kárpáti ◽  
I. Balogh ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Specific Activity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Coagulation Cascade ◽  
Wild Type ◽  
Subunit A ◽  
Coagulation Factor Xiii

SummaryCoagulation factor XIII (FXIII) is a protransglutaminase involved in the last step of the coagulation cascade by stabilising the fibrin clot. Recently, a common variation (FXIII Val34Leu) has been associated with a decreased risk of myocardial infarction and deep venous thrombosis. Val34Leu is critically located near the thrombin activation site of FXIII-A. In this study we investigated its effects on the activation of FXIII. Both recombinant and platelet-derived FXIII Val34Leu variants were shown to be more susceptible to thrombin cleavage than the wild type FXIII. The rate of enzymatic activation of FXIII Val34Leu was found increased, however, the specific activity of fully activated wild type FXIII and the Val34Leu mutant did not differ. During the course of thrombin-induced activation of FXIII fibrin γ-chain dimerisation and α-chain polymerisation developed more rapidly with the Val34Leu mutant. The increased rate of fibrin stabilisation brought about by the Val34Leu FXIII seems to be paradoxically associated with a protective effect against pathological thrombosis. Abbreviations: AP, activation peptide of factor XIII; FXIII, blood coagulation factor XIII; FXIII-A, factor XIII subunit A; FXIII-A’, proteolytically activated subunit A; FXIII-B, factor XIII subunit B; SDS PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis

Coagulation factor XIII deficiency

2014 ◽  
Vol 34 (02) ◽  
pp. 160-166 ◽  
Author(s):  
V. Ivaskevicius ◽  
A. Thomas ◽  
J. Oldenburg ◽  
A. Biswas
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Coagulation Disorder ◽  
Factor Xiii Deficiency ◽  
Disease States ◽  
Coagulation Factor Xiii ◽  
Cross Links ◽  
Bleeding Episodes ◽  
Fxiii Deficiency

SummaryThe plasma circulating zymogenic coagulation factor XIII (FXIII) is a protransglutaminase, which upon activation by thrombin and calcium cross-links preformed fibrin clots/fibrinolytic inhibitors making them mechanically stable and less susceptible to fibrinolysis. The zymogenic plasma FXIII molecule is a heterotetramer composed of two catalytic FXIII-A and two protective FXIII-B subunits. Factor XIII deficiency resulting from inherited or acquired causes can result in pathological bleeding episodes. A diverse spectrum of mutations have been reported in the F13A1 and F13B genes which cause inherited severe FXIII deficiency. The inherited severe FXIII deficiency, which is a rare coagulation disorder with a prevalence of 1 in 4 million has been the prime focus of clinical and genetic investigations owing to the severity of the bleeding phenotype associated with it. Recently however, with a growing understanding into the pleiotropic roles of FXIII, the fairly frequent milder form of FXIII deficiency caused by heterozygous mutations has become one of the subjects of investigative research. The acquired form of FXIII deficiency is usually caused by generation of autoantibodies or hyperconsumption in other disease states such as disseminated intravascular coagulation. Here, we update the knowledge about the pathophysiology of factor XIII deficiency and its therapeutic options.

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