A Hitherto Undescribed Congenital Haemorrhagic Diathesis Probably Due to Fibrin Stabilizing Factor Deficiency

Duckert, F; Jung, Ernst G.; Shmerling, D. H.

doi:10.1055/s-0038-1654918

Cited by 271 publications

(148 citation statements)

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“…The inherited rare genetic variations (most often SNPs) in the Mendelian disorder genes result in defective proteins leading to severe pathologic conditions in either their homo-or heterozygous forms. Examples in the transglutaminase protein family include the life threatening bleeding syndrome as a consequence of any of the more than 70 reported disease causing mutations of FXIIIa (Duckert et al 1960;Karimi et al 2009) and lamellar ichtiosis in cases of TGM1 mutations (Huber et al 1995). No such genetic mutation of TG2 has been reported so far.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions

2011

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Transglutaminase 2 (TG2) is a multifunctional member of an enzyme family: it modifies glutamine residues by cross-linking proteins and incorporating primary amines into them, has protein disulphide isomerase and protein kinase activities, mediates trans-membrane signal transduction and interactions between cell surface proteins and the extracellular matrix. These unusual multiple roles encoded into one polypeptide chain suggest that genomic variations in the TGM2 gene should be limited. Indeed, the available information in databases shows that unlike in the case of most other transglutaminases there are no common single nucleotide polymorphisms in exons of human TGM2. We collected data on and produced some of the rare genetic variants of TGM2 by site directed mutagenesis and found that some were less stable than the most abundant (wild type) enzyme variant and the majority had deficient transamidating activity. Further studies are required to clarify the pathologic significance of these rare TGM2 alleles in the human population.

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Section: Introductionmentioning

confidence: 99%

Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions

2011

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“…Since it was first reported in 1960, more than 200 cases have been reported worldwide [2,3]. Factor XIII plays an integral role in hemostasis by catalyzing the cross linking of fibrin, platelet membrane and matrix protein throughout thrombus formation thus stabilizing the blood clot.…”

Section: Introductionmentioning

confidence: 99%

Factor XIII Deficiency in Siblings: Importance of Prophylactic Replacement

Kini¹,

Chopra²,

Kini³

2011

Indian J Hematol Blood Transfus

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Factor XIII deficiency, an autosomal recessive trait, can result in serious bleeding manifestation. This case report presents two brothers with Factor XIII deficiency. Though the younger sibling had been screened and diagnosed prophylactic replacement therapy had not been initiated unlike the elder brother. He presented with intracranial haemorrhage needing surgical evacuation while the elder brother remained symptom free on regular prophylactic replacement of FFP.

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“…Using amine incorporation as a tool, we have now developed a suitable assay and applied it for studying the inheritance pattern of the fibrin-stabilizing factor deficiency disease (17) and for evaluating transfusion therapy in a totally deficient individual with a severe bleeding disorder. Though studies at Northwestern University now encompass six totally deficient unrelated individuals and their families, the present paper will deal only with the first such case which was initially investigated at Columbia University.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and genetic studies on fibrin-stabilizing factor with a new assay based on amine incorporation

Lóránd¹,

Urayama²,

Kiewiet³

et al. 1969

J. Clin. Invest.

210

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A B S T R A C T Fibrinoligase, the fibrin cross-linking enzyme, transiently appearing during the course of coagulation in normal blood, was shown to catalyze the incorporation of a fluorescent amine, monodansylcadaverine [or N-( 5-aminopentyl) -5-dimethylamino-1-naphthalenesulfonamide] into casein. The reaction provided the basis of a sensitive fluorimetric method for measuring the activity of the enzyme (and also of similar other transpeptidases, such as transglutaminase).In tests involving plasma, certain difficulties had to be overcome which were mainly due to the fact that the enzyme itself does not occur in citrated plasma. Only its precursor (fibrin-stabilizing factor or factor XIII) is present, still requiring limited proteolytic activation by thrombin. Thus, in order to measure amine incorporation with plasma as a source of the factor, thrombin must be added. This necessitated a differential desensitization of the intrinsic fibrinogen so that the latter could not clot and could not thereby interfere with amine incorporation. Also, the thrombin-inactivating capacity of plasma had to be saturated to enable full conversion of the factor to the transpeptidase. Concentrations of casein, monodansylcadaverine, calcium, and hydrogen ions were chosen to permit almost maximal velocity of amine incorporation. A linear relationship with regard to plasma concentration could be obtained only under such conditions. No similar assay is presently available for quantitatively evaluating fibrin-stabilizing factor levels in plasma.

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A Hitherto Undescribed Congenital Haemorrhagic Diathesis Probably Due to Fibrin Stabilizing Factor Deficiency

Cited by 271 publications

References 0 publications

Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions

Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions

Factor XIII Deficiency in Siblings: Importance of Prophylactic Replacement

Diagnostic and genetic studies on fibrin-stabilizing factor with a new assay based on amine incorporation

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