Molecular Analysis Of The Largest Group Of Patients With Factor XIII Deficiency In Southeast Of Iran

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4780-4780 ◽  
Author(s):  
Majid Naderi ◽  
Akbar Dorgalaleh ◽  
Shaban Alizadeh ◽  
Shadi Tabibian ◽  
Taregh Bamedi ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Factor Xiii ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Molecular Characteristics ◽  
Common Mutation ◽  
Factor Xiii Deficiency ◽  
Large Group ◽  
Number Of Patients ◽  
A Subunit

Background Factor XIII deficiency is an extremely rare hemorrhagic disorder with estimated incidence of 1/3000000 million. Sistan and Baluchistan, southeast of Iran has the highest prevalence of disease worldwide. Thus the aim of this study was to assess molecular characteristics of this large group of patients with factor XIII deficiency. Methods This descriptive study was conducted on one hundred and nineteen patients from same number of unrelated families. Genotype analysis for factor XIII subunit A Val34Leu, Tyr204Phe, and Pro564Leu and Trp187Arg was performed for all patients. Results Molecular analysis of this large group of patients with severe factor XIII deficiency revealed that all studied patients were homozygous for TGG CGG mutation at codon 187, in exon 4 of FXIII-A1 gene. Val34Leu, Tyr204Phe, and Pro564Leu FXIII-A subunit gene polymorphisms were not observed in any of patients. In the study population, umbilical cord bleeding, deep soft tissue and hematoma were the most common clinical manifestations and was observed in 82.5%, 53% and 31% respectively. Conclusion Trp187Arg is the most common mutation of FXIII-A subunit in southeast of Iran and probably due to the large number of patients in this area (352 patients), is the most common mutation of factor XIII worldwide. Disclosures: No relevant conflicts of interest to declare.

The PAI-I Gene 4G/5G Polymorphism and Central Nervous System Bleeding In Factor XIII Deficiency

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4782-4782 ◽  
Author(s):  
Majid Naderi ◽  
Akbar Dorgalaleh ◽  
Shaban Alizadeh ◽  
Shadi Tabibian ◽  
Bamedi Taregh ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Control Group ◽  
Severe Bleeding ◽  
Bleeding Tendency ◽  
Intraparenchymal Hemorrhage ◽  
Factor Xiii Deficiency ◽  
History Of ◽  
And Control

Background FXIII deficiency is one of the rare bleeding disorder (RBD) that has a highest incidence in Sistan and Baluchistan province around the world. This disorder represents with different clinical manifestations ranging from mild to severe bleeding tendency including CNS bleeding. The aim of this study is to evaluate the role of PAI-14G/5Gpolymorphism in central nervous bleeding (intra and extracranial hemorrhage) system in factor XIII deficiency. Methods In this case control study was studied 32 FXIII deficient patients with CNS bleeding and also 32 patients with factor XIII deficiency without history of CNS bleeding as control group. Initially both groups were evaluated for the previously reported polymorphism of factor XIII (Trp187Argpolymorphism) in order to confirm their disorder. Then all patients were assessed for PAI-14G/5G polymorphism. Eventually obtained data was analyzed by SPSS software. Results The result of this study revealed that all study patients were homozygote for Trp187Arg polymorphism. We also found that the equal numbers of patients (4 individuals) in case and control groups were heterozygote for PAI-14G/5G polymorphism and none of patients were homozygote for this polymorphism. All heterozygote patients had intracranial hemorrhage and patients with extracranial hemorrhage had no mutation of PAI-14G/5G. Intraparenchymal was the most common site of hemorrhage and was observed in 26 patients (92.8%).We also observed subdural and epidural hemorrhage in two patients (7.1%).Anatomic regions in patients with intraparenchymal hemorrhage, were temporal in nine (32.2%), occipital in eight (28.6%), diffused intraparenchymal hemorrhage in seven (25%), tempro-occipital in two (7.1%) and subdural with temporal in two (7.1%) patients. Conclusion: It seems that PAI-14G/5G polymorphism did not any effect on occurrence of intra and extracranial hemorrhage in patients with factor XIII deficiency. Disclosures: No relevant conflicts of interest to declare.

Seven novel mutations in the factor XIII A-subunit gene causing hereditary factor XIII deficiency in 10 unrelated families

2004 ◽  
Vol 2 (10) ◽  
pp. 1790-1797 ◽  
Author(s):  
A. Vysokovsky ◽  
R. Saxena ◽  
M. Landau ◽  
A. Zivelin ◽  
R. Eskaraev ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Subunit Gene ◽  
Novel Mutations ◽  
Factor Xiii Deficiency ◽  
Hereditary Factor ◽  
A Subunit

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

Association of a Common Polymorphism in the Factor XIII Gene With Venous Thrombosis

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 906-908 ◽  
Author(s):  
Andrew J. Catto ◽  
Hans P. Kohler ◽  
Julie Coore ◽  
Michael W. Mansfield ◽  
Max H. Stickland ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Factor Xiii ◽  
Factor V Leiden ◽  
Common Mutation ◽  
Factor V ◽  
Site Factor ◽  
Gene Coding ◽  
History Of ◽  
Thrombin Activation ◽  
A Subunit

We have shown an association between a common mutation in the factor XIII a-subunit gene, coding for an amino acid change, 3 amino acids from the thrombin activation site (factor XIII Val34Leu) that may protect against myocardial infarction and predisposes to intracranial hemorrhage. To investigate the possible role of factor XIII Val34Leu in the pathogenesis of venous thromboembolism (VTE) and potential interactions with factor V Leiden (FV:Q506) and prothrombin G → A 20210, we studied 221 patients with a history of VTE and 254 healthy controls. Patients with VTE showed an increased frequency of the FXIII Val/Val genotype (63% v 49%) and a lower frequency of the Val/Leu genotype (31% v 42%) than controls (P = .007). FV:Q506 heterozygotes were more frequent in VTE patients (11%) than controls (5%; P = .04). The prothrombin G → A 20210 mutation was present in only 3 patients and no controls (P = .10). In a logistic regression model for a history of VTE, the odds ratio (95% confidence interval) for FXIII Val/Leu or Leu/Leu genotype was 0.63 (0.38 to 0.82) and for possession of FV:Q506 2.40 (1.17 to 4.90). There was no evidence for an interaction between factor XIII Val34Leu genotype and FV:Q506, prothrombin G → A 20210, sex, or age. It is concluded that possession of the Leu allele at factor XIII Val34Leu is protective against deep venous thrombosis.

Physiopathology and Regulation of Factor XIII

2001 ◽  
Vol 86 (07) ◽  
pp. 57-65 ◽  
Author(s):  
Akitada Ichinose
Keyword(s):  
Factor Xiii ◽  
Mrna Level ◽  
Factor Xiii Deficiency ◽  
Specific Expression ◽  
Nonsense Mutations ◽  
B Subunit ◽  
Cell Type Specific Expression ◽  
A Subunit ◽  
Cell Type Specific ◽  
Substrate Proteins

SummaryFactor XIII is a plasma transglutaminase. Transglutaminases are at least 8 enzymes which cross-link a number of proteins. This type of reaction not only enhances the original functions of substrate proteins, but also adds new functions to them. Factor XIII in plasma is a tetramer (A2B2), and the A subunit contains the active site. Although transglutaminases are homologous, the nucleotide sequences in their 5’-flanking region differ significantly. Accordingly, transcription factors play a major role in the cell type-specific expression of each transglutaminase. A variety of missense and nonsense mutations, and deletions/insertions with or without out-of-frame shift/premature termination and splicing abnormalities have been identified in the genes for A and B subunits in factor XIII deficiency. In some cases, the mRNA level of the A or B subunit was severely reduced. Molecular and cellular bases have also been explored by expression experiments and by molecular modeling. In most cases, impaired folding and/or conformational change of the mutant A or B subunit leads to both intra- and extra-cellular instability, which is responsible for factor XIII deficiency.

Biology of Factor XIII and clinical manifestations of Factor XIII deficiency

Transfusion ◽  
2012 ◽  
Vol 53 (5) ◽  
pp. 1120-1131 ◽  
Author(s):  
Jerrold H. Levy ◽  
Charles Greenberg
Keyword(s):  
Factor Xiii ◽  
Clinical Manifestations ◽  
Factor Xiii Deficiency

scholarly journals Phenotype-genotype characterization of 10 families with severe a subunit factor XIII deficiency

2003 ◽  
Vol 23 (1) ◽  
pp. 98-98 ◽  
Author(s):  
Flora Peyvandi ◽  
Liliana Tagliabue ◽  
Marzia Menegatti ◽  
Mehran Karimi ◽  
Istvan Komáromi ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Factor Xiii Deficiency ◽  
A Subunit

Novel Deletion and Insertion Mutations Cause Splicing Defects, Leading to Severe Reduction in mRNA Levels of the A Subunit in Severe Factor XIII Deficiency

1998 ◽  
Vol 79 (03) ◽  
pp. 479-485 ◽  
Author(s):  
Tomonori Izumi ◽  
Utako Nagaoka ◽  
Tetsuo Saito ◽  
Junki Takamatsu ◽  
Hidehiko Saito ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Molecular Mechanisms ◽  
Donor Site ◽  
Pcr Analysis ◽  
Nucleotide Sequence Analysis ◽  
Mrna Levels ◽  
Factor Xiii Deficiency ◽  
Dna And Rna ◽  
Severe Reduction ◽  
A Subunit

SummaryIn order to explore molecular mechanisms for factor XIII deficiency, a patient (Nagoya I) was examined at the DNA and RNA levels. Nucleotide sequence analysis of the patient’s DNA amplified by PCR revealed that he had a 20 bp deletion at the boundary of exon I/intron A, and an insertion of T in the invariant GT dinucleotide at the splicing donor site of exon IV/intron D. The presence of these heterozygous mutations was confirmed by restriction digestion of the amplified fragments of the proband and his parents. RT-PCR analysis demonstrated that only one kind of mRNA without exon IV was detected in Nagoya I, although its level was greatly reduced to less than 5% of normal. The other defective allele of the A subunit gene containing the 20 bp deletion was not detected. Thus, both mutations impaired normal processing of mRNA for the A subunit, resulting in his severe factor XIII deficiency.

Znaczenie kliniczne niedoboru czynnika XIII

2018 ◽  
Vol 22 (3) ◽  
Author(s):  
Izabela Romanowska ◽  
Paweł Łaguna ◽  
Katarzyna Koch ◽  
Michał Matysiak
Keyword(s):  
Factor Xiii ◽  
Clinical Manifestations ◽  
Fresh Frozen Plasma ◽  
Diagnostic Methods ◽  
Screening Tests ◽  
Factor Xiii Deficiency ◽  
Congenital Deficiency ◽  
Fresh Frozen ◽  
Bleeding Episodes ◽  
Frozen Plasma

Factor XIII deficiency is very rare bleeding disorder with an incidence of one per several milions of population. It can be congenital or acquired in several medical conditions, for example in malignancies, autoimmune diseases and after some medications. The level of factor XIII < 5% causes clinical manifestations. It presents not only with mucosal, cutaneous and soft tissue bleeding, poor wound healing but also with intracranial haemorrhage. The congenital deficiency in women is the reason reccurent miscarriages. The diagnosis of factor XIII deficiency requires specialistic tests because routine screening tests are normal. The patients are treated with fresh frozen plasma, cryoprecipitate and FXIII concentrates. We present the latest diagnostic methods for factor XIII deficiency and treatment during bleeding episodes as well as prophylactic procedures.

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