A novel Cys328-terminator mutant implicated in severe coagulation factor XIII deficiency: a case report

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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Post-infectious acute glomerulonephritis and transient coagulation factor XIII deficiency associated with acute parvovirus B19 infection in a young woman

Human Pathology ◽

10.1016/j.humpath.2013.02.011 ◽

2013 ◽

Vol 44 (6) ◽

pp. 1192-1193 ◽

Cited By ~ 1

Author(s):

Stefano Barco ◽

Giampiera Bertolino ◽

Chiara Ambaglio ◽

Filippo Mangione

Keyword(s):

Young Woman ◽

Factor Xiii ◽

Parvovirus B19 ◽

Coagulation Factor ◽

Acute Glomerulonephritis ◽

Factor Xiii Deficiency ◽

Coagulation Factor Xiii ◽

Parvovirus B19 Infection ◽

Post Infectious

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

Haemophilia ◽

10.1111/j.1365-2516.2011.02590.x ◽

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

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A case of coagulation factor XIII deficiency which was diagnosed by examinations immediately before tooth extraction

Oral and Maxillofacial Surgery Cases ◽

10.1016/j.omsc.2021.100214 ◽

2021 ◽

Vol 7 (2) ◽

pp. 100214

Author(s):

Hisataka Kitano ◽

Naoko Koyama ◽

Tomomi Ishikawa ◽

Mamiko Takahashi ◽

Shigehiro Abe ◽

...

Keyword(s):

Factor Xiii ◽

Tooth Extraction ◽

Coagulation Factor ◽

Factor Xiii Deficiency ◽

Coagulation Factor Xiii

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Important roles of the human leukocyte antigen class I and II molecules and their associated genes in the autoimmune coagulation factor XIII deficiency via whole-exome sequencing analysis

PLoS ONE ◽

10.1371/journal.pone.0257322 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0257322

Author(s):

Tsukasa Osaki ◽

Masayoshi Souri ◽

Akitada Ichinose

Keyword(s):

Factor Xiii ◽

Coagulation Factor ◽

Human Leukocyte ◽

Sequencing Analysis ◽

Factor Xiii Deficiency ◽

Leukocyte Antigen ◽

Coagulation Factor Xiii ◽

Whole Exome ◽

Variant Alleles ◽

Fxiii Deficiency

Autoimmune coagulation factor XIII deficiency is a bleeding disorder caused by the formation of autoantibodies against the coagulation factor XIII (FXIII); however, the molecular mechanism underlying this process is unknown. Therefore, in the present study, we aimed to elucidate this mechanism by performing whole-exome sequencing analysis of 20 cases of autoimmune FXIII deficiency. We identified approximately 21,788–23,916 variants in each case. In addition to their ability to activate T cells, present antigens, and immune tolerance, the candidate alleles were further narrowed down according to their allelic frequencies and the magnitude of damage caused by the substitution of amino acids. After selecting 44 candidate alleles, we investigated whether they were associated with the FXIII inhibitory titers and/or the anti-FXIII autoantibodies. We found that two polymorphisms whose variant allele frequencies were significantly lower in the patients tended to decrease FXIII inhibitory titers as the number of variant alleles increased. We also found that five polymorphisms whose variant allele frequencies were significantly higher in the patients tended to increase the levels of the anti-FXIII autoantibodies as the number of variant alleles increased. All of these polymorphisms were found in the human leukocyte antigen (HLA) class I and II molecules and their associated genes. In particular, the HLA class II molecule and its associated genes were found to be involved in the presentation of foreign antigens as well as the negative regulation of the proliferation of T-cells and the release of cytokines. Polymorphisms in the HLA class II molecules and the cytotoxic T lymphocyte antigen 4 have been reported to be associated with the development of autoantibodies in acquired hemophilia A. Therefore, we hypothesized that these polymorphisms may be associated with the development of autoantibodies in autoimmune FXIII deficiency.

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