Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders

Neerman-Arbez, Marguerite; Moerloose, Philippe de; Casini, Alessandro

doi:10.1055/s-0036-1571340

Cited by 84 publications

(43 citation statements)

References 56 publications

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“…Fibrinogen is synthesized in the liver. Decrease in fibrinogen level in this study after amoxicillin overdose could be associated with the hepatotoxic effect of amoxicillin that can cause a decrease in the physiological function of the liver, which includes the production of fibrinogen [20][21][22][23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 76%

“…Fibrinogen is a plasma glycoprotein and an acute phase protein produced by liver cells and the most abundant clotting factor. Plasma fibrinogen is used to determine inherited deficiency, unexplained or prolonged bleeding, and risk of cardiovascular and heart disease [20][21][22][23][24][25][26][27]. Increased fibrinogen concentration can be due to chronic inflammation [20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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Raw Cucumber (Cucumis sativus) Fruit Juice as Possible First-Aid Antidote in Drug-Induced Toxicity

Olaniyan¹,

Ale²,

Uwaifo³

2019

Recent Advances in Biology and Medicine

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Raw cucumber (Cucumis sativus) fruit juice contains substances that have health-benefit potentials. Fibrinogen is produced in the liver cells. Highest concentrations of lactate dehydrogenase (LDH) are found in the liver, heart, and skeletal muscle, and alanine transaminase (ALT) is a liver enzyme. Overdose of amoxicillin, an antibiotic, can lead to hemolysis, hepatotoxicity, and inflammation. This study was therefore designed to determine the use of raw cucumber (C. sativus) fruit juice as a possible first-aid antidote in druginduced toxicity. Fifteen rabbits of the same gender weighing 0.9-1.4 kg were used for the study. They were divided into three groups of five rabbits each as follows: Group A—five control rabbits; Group B—five rabbits, given 30.0 mg/kgBW subcutaneous injection of amoxicillin every 24 h for seven days and was followed by 30 mL raw cucumber fruit juice supplementation for 14 days; Group C—five rabbits, given 30.0 mg/kgBW subcutaneous injection of amoxicillin every 24 h and raw cucumber fruit juice supplementation for 14 days simultaneously. Plasma LDH, ALT, and fibrinogen were determined in the rabbits by spectrophotometry. There was a significant increase in plasma ALT and LDH and a significant decrease in fibrinogen following amoxicillin overdose compared with the results obtained from the basal samples and the control rabbits. These abnormalities were reversed when raw cucumber fruit juice was administered to the experimental rabbits initially overdosed with amoxicillin (ρ < 0.05). There was a significant increase in the plasma value of LDH in the rabbits when they were supplemented with raw cucumber fruit juice following amoxicillin overdose and when the rabbits were coadministered with raw cucumber fruit juice and amoxicillin overdose compared with their basal samples (ρ < 0.05). There was no significant difference in the plasma value of ALT and fibrinogen when the rabbits were coadministered with raw cucumber fruit juice (ρ > 0.05). This study showed an increase in plasma ALT and LDH, and a decrease in fibrinogen following the administration of subcutaneous injection of amoxicillin; however, these abnormalities were reversed when the rabbits were administered 30 mL of raw cucumber fruit juice. Raw cucumber fruit juice could be applied as first-aid antidote in drug induced toxicity.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Raw Cucumber (Cucumis sativus) Fruit Juice as Possible First-Aid Antidote in Drug-Induced Toxicity

Olaniyan¹,

Ale²,

Uwaifo³

2019

Recent Advances in Biology and Medicine

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“…[ 4 ] Fibrinogen is a plasma glycoprotein composed of 2964 amino acids, forming a symmetrical hexameric structure (Aα, Bβ, γ) 2 , [ 5 ] which is encoded by 3 fibrinogen genes: FGA, FGB, and FGG; thus, the heterozygous missense mutations existing in most patients occur in 1 of the 3 genes, [ 6 ] and these mutation sites are mainly located on the exon 2 of FGA and exon 8 of FGG. Research suggests CD is responsible for thromboembolic phenomena, bleeding, or both of them, while more than a few patients are asymptomatic, [ 7 ] but the risk of bleeding or thrombosis is higher than that of normal people; moreover, CD patients may suffer from obstetric complications, such as placental abruption, spontaneous abortion, and so on. In this paper, the phenotypic and genotypic analysis of a family with CD was conducted to preliminarily explore the pathogenesis of CD in the family that we discovered.…”

Section: Introductionmentioning

confidence: 99%

A novel fibrinogen variant in a Chinese pedigree with congenital dysfibrinogenemia caused by FGA P. Arg38Thr mutation

Cai

Wang

et al. 2018

Medicine

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Rationale:Congenital dysfibrinogenemia (CD) is characterized by altered functional properties of the fibrinogen; people who suffer from CD often have a low activity of fibrinogen and the mutation in the genomic DNA.Patient concerns:A 6-year-old child was examined with a low activity of fibrinogen measured by Von Clauss method and PT-derived method which indicated a normal level of fibrinogen; this abnormality was also detected in her mother. The genomic DNA of all the family members was extracted, and all exons of 3 fibrinogen genes which encode fibrinogen alpha chain (FGA), fibrinogen beta chain (FGB), and fibrinogen gamma chain (FGG) were amplified by polymerase chain reaction (PCR), in addition, sanger sequencing, homologous sequence alignment and bioinformatics software were performed for the further analysis.Diagnoses:CD in this pedigree is associated with c.113G>C in the exon 2 of FGA which caused Arg38Thr mutation.Outcomes:The child and her mother showed a low plasma concentration of fibrinogen measured by Von Clauss method, whereas a normal result measured by PT-derived method; finally, c.113G>C in the exon 2 of FGA was detected in the pedigree which caused Arg38Thr mutation and it is the first report on a pedigree with CD caused by AαArg38Thr.Lessons:This case gives us the lesson that not all patients with CD showed typical symptoms and laboratory test results; the result of fibrinogen concentration and antigen which is tested by Von Clauss method and immunoturbidimetric assay is various according to the condition of each CD patient.

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“…Inherited fibrinogen disorders can be quantitative (Type I; absence or decreased level of circulating fibrinogen, afibrinogenemia and hypofibrinogenemia, respectively) or qualitative (Type 2; normal or decreased antigenic levels and low fibrinogen activity, dysfibrinogenemia and hypodysfibrinogenemia, respectively) [ 2 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Dysfibrinogenemia is caused by structural abnormalities that can be inherited (congenital) or acquired [ 5 ]. Inherited dysfibrinogenemia is caused by mutations in the coding region of the fibrinogen Aα, Bβ or γ genes and the majority of cases result from heterozygous missense mutations [ 4 ]. The prevalence of inherited dysfibrinogenemia in the general population is unknown [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

A novel fibrinogen mutation: FGA g. 3057 C > T (p. Arg104 > Cys) impairs fibrinogen secretion

et al. 2017

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BackgroundAbnormal fibrinogens can be caused by clinically silent hereditary mutations. A new case was detected accidentally in an 11-year-old girl when routine pre-operative coagulation tests were performed for nasal turbinate surgery.MethodsThe fibrinogen genes FGA, FGG and FGB were sequenced using standard protocols. The kinetics of fibrin formation were followed by turbidity at 350 nm. Purified fibrinogen was incubated with plasmin, and the degradation products analyzed by SDS/PAGE. The formation of fibrinogen-albumin complexes was analyzed by immunobloting. Fibrin structure was examined in a Nikon Eclipse TE 2000-U laser microscope. Secretion of the variant protein was analyzed directly by reverse phase-electrospray time of flight-mass spectrometry (TOF-MS).ResultsDNA sequencing revealed a novel heterozygous g. 3057 C > T mutation in the FGA that predicts a p. Arg104 > Cys substitution, in the proband and her father. Both patients were asymptomatic with low functional and antigen fibrinogen concentrations. The proband’s plasma fibrinogen polymerization was almost normal, with a 12% decrease in the final turbidity, while, the father’s fibrin formation had a diminished slope and final turbidity (2.5× and 40%, respectively). Aα Arg104 is located at a plasmin cleavage site in the coiled-coil region of fibrinogen. However, the father’s fibrinogen plasmin degradation was normal. Although the exchanged Cys introduces an unpaired –SH, immunoblotting showed no fibrinogen-albumin complexes. Furthermore, the plasma clot structure observed by confocal microscopy appeared almost normal. TOF-MS showed that the variant Aα chain was underrepresented in plasma and made up only about 25% of the total.ConclusionsThe low expression of the Aα Arg104 > Cys chain in circulation could account for the observed hypodysfibrinogenemia.Electronic supplementary materialThe online version of this article (10.1186/s12878-017-0086-8) contains supplementary material, which is available to authorized users.

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Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders

Cited by 84 publications

References 56 publications

Raw Cucumber (Cucumis sativus) Fruit Juice as Possible First-Aid Antidote in Drug-Induced Toxicity

Raw Cucumber (Cucumis sativus) Fruit Juice as Possible First-Aid Antidote in Drug-Induced Toxicity

A novel fibrinogen variant in a Chinese pedigree with congenital dysfibrinogenemia caused by FGA P. Arg38Thr mutation

A novel fibrinogen mutation: FGA g. 3057 C > T (p. Arg104 > Cys) impairs fibrinogen secretion

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