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1.
Acta méd. costarric ; 65(2): 92-96, abr.-jun. 2023. tab, graf
Article in Spanish | LILACS, SaludCR | ID: biblio-1556684

ABSTRACT

Resumen La deficiencia congénita de factor VII es uno de los desórdenes congénitos de la coagulación más comunes, con una prevalencia a nivel mundial de 1:300,000- 1:500,000. Se presenta el caso de un paciente masculino de 37 semanas y 5 días, nacido por cesárea intraparto y con el antecedente heredofamiliar de muerte de hermano a los 4 días de nacido por hemorragia intracraneal, quien a los 14 días de nacido es llevado a emergencias por sangrado umbilical que persistía después del desprendimiento del cordón. Su abordaje inicial incluyó la toma de tiempos de coagulación, lo que mostró alteración del tiempo de protrombina con tiempo de tromboplastina parcial y fibrinógeno normales. El sangrado, así como el tiempo de protrombina prolongado, persistió a pesar de que se administrara vitamina K en tres ocasiones y de transfundir plasma fresco congelado. Se sospechó defecto congénito de factor VII, que se confirmó con la cuantificación del factor. A los 2 meses y 10 días de edad, se le realizaron estudios moleculares basados en secuenciación masiva de nueva generación (NGS por sus siglas en inglés). El análisis determinó dos variantes heterocigotas: F7, intrón 5, c.430+1G>A y F7, intrón 8, c.805+1G>A. Actualmente, el paciente se maneja con profilaxis 5 días de la semana con factor VII recombinante 200 µg/día intravenoso (280 µg/kg) sin recurrencia de sangrados.


Abstract Factor VII congenital deficiency is one of the most common congenital deficiencies of the blood system, with a worldwide prevalence of 1:300,000- 1:500,000. Here we describe a male patient, born by C section, with the family history of death at 4 days old of a sibling caused by intracranial hemorrhage, who presented bleeding at the umbilical cord site at 14 days old, even after falling of the cord. The initial assessment included laboratory tests with coagulation times revealing prolonged prothrombin time, with normal partial thromboplastin time as well as fibrinogen. The bleeding and the prolonged prothrombin time persisted despite the administration of vitamin K in three doses as well as fresh frozen plasma. Congenital defect of factor VII was suspected and later confirmed by measuring the factor. At the age of 2 months and 10 days, molecular studies based on next-generation massive sequencing (NGS) were performed. The analysis exhibited two heterozygous variants: F7, intron 5, c.430+1G>A y F7, intron 8, c.805+1G>A. Currently the patient is receiving prophylaxis 5 days per week with recombinant factor VII 200 µg/ day intravenous (280 µg/kg) with no recurrent bleeding.


Subject(s)
Humans , Male , Infant , Intracranial Hemorrhages/diagnosis , Factor VII Deficiency/diagnosis , Costa Rica , Heredity
2.
Rev. colomb. anestesiol ; 49(1): e600, Jan.-Mar. 2021. graf
Article in English | LILACS, COLNAL | ID: biblio-1149800

ABSTRACT

Abstract Introduction Glanzmann thromboasthenia is a rare congenital bleeding disorder caused by a mutation in platelet glycoprotein α-IIb and β3 encoding genes (ITGA2B; 607759 and ITGB3; 173470) in chromosomes I7q21.31 and 17q21.32, respectively, which results in a qualitative or quantitative alteration of the platelet integrin αIIbβ3 (glycoprotein IIb/IIIa) receptor. Glanzmann thromboasthenia is classified as type I when less than 5% of glycoprotein αIIbβ3 is expressed, and as type II when more than 5% is expressed. Case presentation Description of the perioperative management of a 13-year-old female patient with Glanzmann thromboasthenia who underwent endoscopic anterior bilateral ethmoidectomy. Management was centered on prophylactic platelet transfusion plus the use of tranexamic acid, as well as thromboelastographic determination of hemostasis. There were no bleeding complications during or after the procedure. Conclusiones Pediatric patients with Glanzmann thromboasthenia are at a high risk of perioperastive bleeding. Platelet transfusion is the best prophylactic and therapeutic alternative; however, even in the absence of anti-platelet antibodies, it may not be effective, and viscoelastic testing must be used for assessment during the surgical procedure in order to improve patient safety.


Resumen Introducción La trombastenia de Glanzmann es un trastorno hemorrágico congénito infrecuente, causado por mutación en los genes que codifican las glucoproteínas plaquetarias α-IIb (ITGA2B; 607759) y β3 (ITGB3; 173470) en los cromosomas I7q2i.3i y I7q2i.32, respectivamente, alterando cualitativa o cuantitativamente al receptor plaquetario de integrina αIIbβ3 (glucoproteína IIb/IIIa). La trombastenia de Glanzmann se clasifica como tipo I cuando se expresa menos del 5 % de la glucoproteína αIIbβ3 y como tipo II, cuando es mayor al 5 %. Presentación del caso Se describe el manejo perioperatorio de una paciente de 13 años de edad con trombastenia de Glanzmann, sometida a etmoidectomía anterior bilateral endoscópica. El manejo se centró en la transfusión profiláctica de plaquetas y ácido tranexámico, así como en la evaluación de la hemostasia con tromboelastografía. No hubo complicaciones hemorrágicas durante y después del procedimiento. Conclusiones Los pacientes pediátricos con trombastenia de Glanzmann tienen alto riesgo de hemorragia perioperatoria. La transfusión de plaquetas es la mejor alternativa profiláctica y terapéutica; sin embargo, incluso en ausencia de anticuerpos antiplaquetarios, puede no ser efectiva y debe evaluarse mediante pruebas viscoelásticas durante los procedimientos quirúrgicos para mejorar la seguridad del paciente.


Subject(s)
Humans , Female , Adolescent , Thrombasthenia , Factor VIIa , Thrombelastography , Platelet Transfusion , Factor VII Deficiency , Genetic Diseases, Inborn
3.
Article in Chinese | WPRIM | ID: wpr-775764

ABSTRACT

OBJECTIVE@#To explore molecular etiology and clinical characteristics of two pedigrees affected with hereditary factor VII(FVII) deficiency.@*METHODS@#The nine exons and flanking sequences of the F7 gene of the probands were amplified by PCR. The amplicons were analyzed by direct sequencing. Suspected mutations were subjected to SWISS-MODEL modeling and analysis of protein structure change by Pymol software and conservation of amino acids across various species.@*RESULTS@#For proband of pedigree 1, the prothrombin time (PT), FVII activity (FVII:C) and FVII antigen (FVII:Ag) were 36.3 s, 3%, 53.56%, respectively. Sequencing revealed a compound heterozygous variants of c.80_81delCT and c.1371G>T(p.Arg439Ser). His son carried a heterozygous c.1371G>T (p.Arg439Ser) variant. For proband of pedigree 2, the PT, FVII:C and FVII:Ag were 22.3 s, 4%, 1.58%, respectively. Sequencing has revealed a compound heterozygous c.278G>T(p.Arg75Met) missense variant in exon 3 and c.1278T>G (p.His408Gln) in exon 9 of the F7 gene. His mother and son both carried a heterozygous c.278G>T(p.Arg75Met) variant. Three-dimensional simulation and homology analysis revealed that the p.Arg439Ser and p.Arg75Met can respectively alter part of hydrogen bonds and two highly conserved amino acids.@*CONCLUSION@#Two novel heterozygous missense variants of the F7 gene [c.1371G>T(p.Arg439Ser) and c.278G>T(p.Arg75Met)] probably account for the decrease of factor VII in the two pedigrees.


Subject(s)
Humans , Asian People , Factor VII , Factor VII Deficiency , Genotype , Heterozygote , Mutation , Pedigree
4.
Article in Chinese | WPRIM | ID: wpr-776756

ABSTRACT

OBJECTIVE@#To detect potential mutations of the coagulation factor Ⅶ (F7) gene in a pedigree affected with hereditary FⅦ deficiency and explore its molecular pathogenesis.@*METHODS@#The FⅦ antigen (FⅦ:Ag) was analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Prothrombin time (PT), FⅦ activity (FⅦ:C) and other coagulant parameters were quantified with an one-stage clotting assay. The F7 gene was amplified by PCR and sequenced. Mutational sites were confirmed by reverse sequencing. Impact of amino acid substitution was assessed using SIFT and PolyPhen-2 software. Structure of the mutant protein was analyzed using Swiss-pdb Viewer software based on the three-dimensional structure in the Protein Data Bank.@*RESULTS@#The propositus had prolonged PT (36.3 s), with FⅦ:C and FⅦ:Ag significantly reduced to 2% and 44%, respectively. Her father, mother, younger sister and daughter had slightly prolonged PT and reduced FⅦ:C (86%-120%). The FⅦ:Ag of her father and younger sister were also reduced. DNA sequencing revealed that the propositus has carried compound heterozygous mutations (Lys341Glu and IVS6-1G>A) of the F7 gene. Her father and younger sister were heterozygous for the IVS6-1G>A mutation, while her mother and daughter were heterozygous for the Lys341Glu mutation. Bioinformatics analysis indicated that Lys341Glu mutation may affect the stability and function of the FⅦ protein.@*CONCLUSION@#The Lys341Glu and IVS6-1G>A mutations probably underlie the reduced activity of FⅦ in this pedigree.


Subject(s)
Female , Humans , Male , Factor VII , Genetics , Factor VII Deficiency , Genetics , Genetic Testing , Heterozygote , Mutation , Pedigree
5.
Article in Chinese | WPRIM | ID: wpr-771864

ABSTRACT

OBJECTIVE@#To investigate the gene mutations types and the clinical characteristics in 3 patients with hereditary coagulation factor Ⅶ deficiency.@*METHODS@#The phenotype diagnosis was validated by detecting the coagulation parameters including prothrombin time (PT),activated partial thromboplastin time (APTT), fibrinogen (FIB), FⅦ activity (FⅦ: C) and specific antigens (FⅦ: Ag) of proband and its family members. All exons, exon-intron boundaries, 5' untranslated regions and 3' untranslated regions of F7 gene were amplified with PCR. Potential mutations were detected by direct sequencing of purified PCR products. Suspected mutations were confirmed by sequencing of the opposite strand.@*RESULTS@#A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency and family members, including 4 misssense mutations and 1 splice site mutation. Out of 3 cases of hereditary coagulation factor Ⅶ deficiency 2 had double heterozygous mutation, I had homozygous mutations. Patient 1 had p.His408Gln with p.Arg413Gln double heterozygous mutations, her sister had p.His408Gln with p.Arg413Gln double heterozygous mutations, another one had p.His408Gln mono-heterozygous mutation, their correspo FⅦ: C were 5%, 3%, 75%. Patient 2 had p.Arg364Gln with p.His408Gln double heterozygous mutations, her brother had p.Arg364Gln with IVS6-1G>A double heterozygous mutations, their corresponding FⅦ: C were 2.0%, 2.0%. Patient 3 had p.Arg337Cys homozygous mutation, FⅦ: C was 3.0%.@*CONCLUSION@#A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency, the p.His408Gln is a common mutation, the FⅦ: C and FⅦ: Ag have no correlation with clinical phenotypes.


Subject(s)
Female , Humans , Male , Factor VII , Factor VII Deficiency , Heterozygote , Homozygote , Mutation , Pedigree , Phenotype
6.
Article in Spanish | LILACS | ID: biblio-1013825

ABSTRACT

RESUMEN No hay guías específicas para el manejo de pacientes embarazadas con la deficiencia de Factor VII; no hay una correlación entre el nivel de FVII y el riesgo de hemorragia y el nivel del Factor VII aumento durante el embarazo. Presentamos un caso clínico, el manejo y las recomendaciones del consenso.


Subject(s)
Humans , Female , Pregnancy , Young Adult , Pregnancy Complications, Hematologic/diagnosis , Factor VII Deficiency/diagnosis , Pregnancy Complications, Hematologic/therapy , Blood Transfusion , Pregnancy Outcome , Cesarean Section , Factor VII Deficiency/congenital , Factor VII Deficiency/therapy , Hemorrhage/etiology
7.
Article in Chinese | WPRIM | ID: wpr-690958

ABSTRACT

<p><b>OBJECTIVE</b>To examine one young female patient with hereditary FVII deficiency and her family members, to observe the gene mutation and clinical phenotype, and to investigate the molecular mechanism of the dysfunction.</p><p><b>METHODS</b>Prothrombin time (PT), activated partial thromoploastin time (APTT), fibrinogen (Fg) and FVII activity (FVII:C) and FVII antigen (FVII:Ag) were tested. The gene mutations were sought by DNA sequencing for all of the exons and flanks, 5' and 3' non-translation region of F7 gene. To confirm the role of the found gene mutation, the reverse sequence were determined with Chromas software. To infer the influence of the mutation on the synthesis and function of FVII protein, the FVII protein molecule model containing the found mutation was constructed and the function prediction was performed by the signal peptide prediction database.</p><p><b>RESULTS</b>Compared with the normal population, the proband's PT value was significantly prolonged, and the ratio % FVII:C and that of FVII:Ag were significantly decreased by 1.1% and 0.9%, respectively. The PT, APTT, FVII:C and FVII:Ag of the proband's parents were both normal. Heterozygous 556th nucleotide mutations T/G were found in the proband's and his father's exon lA of F7 gene, with codon CTG turning into CGG, corresponding leucine (L) into arginine (R), i.e Leu12Arg. Function prediction showed that L12R mutations affected the segmentation of different parts of the signal peptide and its corresponding function, which could result in the decline in the mature protein synthesis and its activity obviously. In addition, a spontaneous 3' untranslated region c11814-insAA heterozygous mutation was detected in the proband's F7 gene, while her parents didn't possess this mutation.</p><p><b>CONCLUSION</b>A new hererozygous mutation (L12R) located in signal peptide of F7 gene is the primary molecular basis of the case with hereditary FVII deficiency. At the same time, the proband's spontaneous 3' non-translation region c11814-insAA mutation may lead to the further reduetion of the FVII synthesis.</p>


Subject(s)
Female , Humans , Factor VII , Factor VII Deficiency , Mutation , Pedigree , Phenotype , Protein Sorting Signals
8.
Rev. Nac. (Itauguá) ; 9(2): 46-66, 2017.
Article in Spanish | LILACS, BDNPAR | ID: biblio-884649

ABSTRACT

Introducción: la hemostasia es el conjunto de sistemas que actúan coordinadamente para mantener la integridad de los vasos sanguíneos y la fluidez de la sangre; la alteración puede desencadenar trastornos trombóticos o hemorrágicos, dependiendo de la naturaleza de la falla. Objetivos: describir las coagulopatías hemorrágicas que se registraron en el departamento de laboratorio del Hospital Nacional de Itauguá, desde julio 2014 hasta diciembre 2015, obtener frecuencia y datos demográficos, edad, sexo, procedencia y clasificar las coagulopatías según deficiencias de factores de la coagulación, vía extrínseca, vía intrínseca y vía común final; sospecha de inhibidores adquiridos y enfermedad de von Willebrand. Material y Métodos: diseño observacional, descriptivo, retrospectivo de corte trasverso; incluyéndose pacientes de ambos sexos, todas las edades, derivados de médicos hematólogos. Resultados: se registraron 77 pacientes con coagulopatías hemorrágicas en el Laboratorio, 43 fueron del sexo masculino, de 1 a 75 años, mediana 18 años; 31% (24/77) con deficiencias del factor VII, todos leves, edades 7 a 75 años. En la vía intrínseca, la deficiencia del factor VIII o Hemofilia A, fue la más observada 29%(22/77), mayoría severas (13/22), mientras que déficit de factor IX, Hemofilia B, en 4 pacientes 5%(4/77). 85% Hemofilia A y 15% Hemofilia B, edades 1 y 64 años, mediana 13,5 años, todos del sexo masculino; no se registraron deficiencias de FXI y FXII en el periodo de estudio. De la vía común final, se encontraron 3 pacientes con hipofibrinogenemia, 1 con probable disfibrinogenemia, 1 con déficit de Factor II, 2 de Factor V y 2 de Factor X, 2 adultas, y el resto pediátricos; estas deficiencias son muy poco frecuentes, Factor I, V y X de 1/1.000.000 y FII 1/2.000.000 personas. Quince pacientes con sospecha de inhibidores, dos de ellas con inhibidor específico anti-FVIII, y probables inhibidores de interferencia. Se confirmó el primer déficit de factor Von Willebrand, en una mujer de 47 años. Conclusiones: entre las coagulopatías hemorrágicas de mayor frecuencia, se encuentran las Hemofilias A y B, seguida de deficiencias del factor VII y probables inhibidores de interferencia, los dos casos de inhibidores específicos anti Factor VIII fueron en pacientes con Hemofilia A severa. Fue relevante también el hallazgo de deficiencias de la vía común de la coagulación, a pesar de ser poco frecuentes. Algunos pacientes fueron diagnosticados en edad adulta, reflejando lo tardío que se llega al diagnóstico en el país.


Introduction: hemostasis is the set of systems that work in concert to maintain the integrity of blood vessels and blood flow; alteration can trigger thrombotic disorders or bleeding, depending on the nature of the fault Objective: describe hemorrhagic coagulopathy registered in the Medical Laboratory Department diagnosis at the National Hospital of Itauguá, from July 2014 to December 2015, obtain frequency and demographics, age, sex, origin and classify coagulopathy in to deficiencies of coagulation factors of the extrinsic pathway, intrinsic pathway, and common pathway; suspicion acquired inhibitors and von Willebrand's disease. Material and Methods: the design was an observational, descriptive, retrospective cross sectional study; being including patients of both sexes, all ages, referred by hematologists. Results: 77 patients with hemorrhagic coagulopathies, were female 43 male and 34 female, from 1 to 75 years, median age of 18 years; 31% (24/77) with factor VII deficiency, all mild, ages 7 to 75, 1 / 500,000 appears. In the intrinsic pathway, the factor VIII deficiency or hemophilia A, was the most observed 29% (22/77) severe majority (13/22), while Factor IX deficit, Hemophilia B, in 5% of patients (4/77). 85% Hemophilia A, and 15% Hemophilia B, ages 1 to 64 years, median age of 13.5 years, all male; no FXI and FXII deficiencies were recorded in the study period.Of the final common pathway, 3 patients with hipofibrinogenemia were found, 1 probable dysfibrinogenaemia, 1 deficiency of FII, 2 FV and FX 2, 2 were adult and the rest were pediatric; these deficiencies are rare, FI, V and X of 1 / 1,000,000 and FII 1 / 2,000,000 people. Fifteen patients with suspected inhibitors adquired, two of them with anti-FVIII specific inhibitor, and probable interference inhibitors. The first von Willebrand, factor deficiency was confirmed in a woman of 47 years. Conclusions: among the most frequent hemorrhagic coagulation disorders, we found hemophilia A and B, followed by deficiencies of factor VII and probable interference inhibitors both cases of specific inhibitors of factor VII were found in patients with severe Hemophilia A. Some patients were diagnosed in adulthood


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Young Adult , Coagulation Protein Disorders/diagnosis , von Willebrand Diseases/diagnosis , Cross-Sectional Studies , Retrospective Studies , Hemophilia B/diagnosis , Blood Coagulation Disorders, Inherited/diagnosis , Factor VII Deficiency/diagnosis , Hemophilia A/diagnosis
9.
Article in Chinese | WPRIM | ID: wpr-247673

ABSTRACT

<p><b>OBJECTIVE</b>To provide mutation analysis and prenatal diagnosis for a family affected with congenital factor VII(FVII) deficiency.</p><p><b>METHODS</b>DNA was extracted from peripheral blood samples from the proband and his parents. All exons and flanking sequence of the FVII gene were amplified with PCR and subjected to direct sequencing. Prenatal diagnosis was performed by amniocentesis.</p><p><b>RESULTS</b>A homozygous mutation (NM_000131.3) c.572-1G>A was identified in the proband. Both parents of the fetus were carriers of the mutation.</p><p><b>CONCLUSION</b>A method for molecular diagnosis of congenital factor VII deficiency was established and successfully applied for an affected family.</p>


Subject(s)
Humans , Infant, Newborn , Male , Factor VII Deficiency , Genetics , Mutation , Prenatal Diagnosis
10.
Article in Korean | WPRIM | ID: wpr-112436

ABSTRACT

Congenital factor VII deficiency is a rare hemorrhagic disorder, and invasive procedures are likely to cause excessive bleeding in these patients. Endoscopic submucosal dissection (ESD) has been accepted as a curative treatment modality for gastric adenoma, early gastric cancer (EGC) and any other mucosal and submucosal tumors. The most important complications of ESD are bleeding and perforation. The use of antiplatelet agents or coagulopathies are risk factors for these complications. There are only few reports of successful ESD with coagulation disorders. We report a case of a 70-year-old female patient who was diagnosed with a gastric adenoma and factor VII deficiency. The patient was successfully treated with ESD. Before ESD, recombinant Coagulation factor VIIa was injected, and the procedure was performed successfully without any complications. In conclusion, ESD can be performed successfully in patients with factor VII deficiency, when recombinant human factor VIIa is administered properly.


Subject(s)
Aged , Female , Humans , Adenoma , Endoscopy , Factor VII Deficiency , Factor VIIa , Hemorrhage , Hemorrhagic Disorders , Platelet Aggregation Inhibitors , Risk Factors , Stomach Neoplasms
11.
Article in Chinese | WPRIM | ID: wpr-239500

ABSTRACT

<p><b>OBJECTIVE</b>To identify potential mutations in a family affected with inherited factor Ⅶ (FⅦ) deficiency.</p><p><b>METHODS</b>Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FⅦ activity (FⅦ:C) and other coagulant parameters of the proband and 15 family members were measured. Potential mutations were screened in the pedigree by polymerase chain reaction and direct DNA sequencing.</p><p><b>RESULTS</b>The PT of the proband and his younger brother was significantly prolonged to 39.0 s and 30.1 s, respectively. FⅦ:C of the proband and his younger brother was obviously reduced to 2% and 3%, respectively. FⅦ:C of his grandmother, maternal grandmother, aunt, father, mother, maternal uncle and maternal aunt was all below the normal range (80%-108%), which measured 68%, 54%, 71%, 73%, 62%, 72% and 59%, respectively. The other coagulant parameters were in the normal range. Two heterozygous mutations, g.11349G>A and g.11482T>G, both reside in exon 8 of the F7 gene, have resulted in p.Arg304Gln and p.His348Gln substitutions, were identified in the proband. The same mutations were also found in the proband's younger brother. Four maternal members in this family (grandmother, mother, maternal uncle and maternal aunt of the proband) were heterozygous for the p.Arg304Gln mutation, while three paternal members (grandmother, aunt and father of the proband) were heterozygous for the p.His348Gln mutation.</p><p><b>CONCLUSION</b>The proband had inherited two independent mutations of the F7 gene including g.11349G>A and g.11482T>G from his mother and father, respectively. The compound heterozygous mutation probably explains the low FⅦ concentrations in this pedigree.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Base Sequence , Blood Coagulation Tests , Factor VII , Genetics , Metabolism , Factor VII Deficiency , Blood , Genetics , Genetic Testing , Molecular Sequence Data , Pedigree
12.
Article in English | WPRIM | ID: wpr-37129

ABSTRACT

Factor VII (FVII) deficiency is an infrequent hereditary bleeding disorder that can make excessive bleeding in surgical interventions, such as a postpartum hemorrhage in a cesarean section. Although a recombinant form of activated FVII has been applied for bleeding control in FVII-deficient patients, its applications in the field of obstetrics are still limited, especially in Korea. Replacement of blood products is still preferred as first-line therapy, with antifibrinolytic agents used as adjunctive therapy. We report herein the case of a successful cesarean section in an 18-year-old woman with FVII deficiency.


Subject(s)
Adolescent , Female , Humans , Pregnancy , Antifibrinolytic Agents , Cesarean Section , Factor VII , Factor VII Deficiency , Hemorrhage , Korea , Obstetrics , Postpartum Hemorrhage
13.
Article in Chinese | WPRIM | ID: wpr-254518

ABSTRACT

<p><b>OBJECTIVE</b>To identify potential mutations and explore the molecular mechanism underlying combined inherited coagulation factors VII(FVII) and X(FX) deficiency for a family featuring consanguineous marriage between maternal cousins.</p><p><b>METHODS</b>Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FVII activity (FVII:C), FX activity (FX:C), FVII antigen (FVII:Ag), FX antigen (FX:Ag) and other coagulant parameters of the proband and 5 family members were measured. Potential mutations in exons, exon-intron boundaries and 5', 3' untranslated sequences of F7 and F10 genes were screened by polymerase chain reaction and direct sequencing. Suspected mutations were confirmed by sequencing the opposite strand.</p><p><b>RESULTS</b>PT and APTT of the proband were obviously prolonged to become 76.4 s and 60.2 s, respectively. FVII:C, FVII:Ag,FX:C and FX:Ag of the proband were obviously reduced to become 4%, 6%, 6% and 33%, respectively. Both PT and APTT of her grandmother, father, mother and daughter were slightly prolonged, which have measured 16.4 s, 15.8 s,16.9 s, 16.5 s, and 44.0 s, 42.1 s, 41.1 s, 43.5 s, respectively. And their FVII:C (34%, 39%, 31%, 40%, respectively), FX:C (50%, 58%, 47%, 42%, respectively) and FX:Ag (51%, 54%, 58%, 47%, respectively) were slightly reduced, while FVII:Ag was in the normal range. The coagulant parameters of her younger brother were within normal range. Two homozygous mutations, g.11267C to T in exon 8 of F7 gene, which resulted in an Arg277Cys substitution, and g.28139G to T in exon 8 of F10 gene which led to a Val384Phe substitution, were identified in the proband. The proband's grandmother, parents and daughter were heterozygous for both Arg277Cys and Val384Phe mutationss. Wild-type alleles of both F7 and F10 genes were also found in the younger brother.</p><p><b>CONCLUSION</b>A homozygous Arg277Cys mutation and a Val384Phe mutation have been respectively identified in the F7 and F10 genes, which can explain the low levels of FVII and FX in this family. The former has been inherited from the consanguineous parents.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Consanguinity , Factor VII Deficiency , Genetics , Factor X Deficiency , Genetics , Genotype , Mutation , Pedigree , Phenotype
14.
Article in Chinese | WPRIM | ID: wpr-237293

ABSTRACT

<p><b>OBJECTIVE</b>To identify and characterize a missence mutation Ser250 Phe underlying coagulation factor Ⅶ (FⅦ) deficiency in a Chinese patient and his family.</p><p><b>METHODS</b>The FⅦ gene (F7) was analyzed by DNA sequencing, and the FⅦ levels (including antigen and activity) in patient's plasma were determined with enzyme-linked immunoabsorbent assay (ELISA) and one stage prothrombin time based method. In addition, a FⅦ-250 Phe mutant corresponding to the identified mutation was expressed in HEK293 cells, and a subcellular localization experiment in CHO cells was performed to clarify the molecular mechanism of FⅦ deficiency caused by the FⅦ-250 Phe mutation.</p><p><b>RESULTS</b>The patient had a prolonged prothrombin time (PT: 36.5 s) and low levels of both FⅦ antigen and activity (130.2 ng/mL and 4.0%, respectively). Two heterozygous mutations were identified in the F7 gene (NG-009262.1), which included a g.15975 G>A mutation at the splice receptor site of intron 6 (IVS6-1G>A) and a novel g.16750 C>T mutation in exon 8, which resulted in replacement of Ser (TCC) 250 with Phe (TTC)250 in the vicinity of a charge-stablizing system. By gene expression experiments, the antigen and activity levels of FⅦ-250 Ser and FⅦ-250 Phe in the culture medium were (37.77 ± 2.30) ng/mL and (4.02 ± 0.52) ng/mL, respectively. ELISA and Western blotting analyses indicated that expression of the mutant FⅦ-250 Phe and wild type FⅦ-250 Ser was (130.51 ± 2.32) ng/mL and (172.45 ± 2.25) ng/mL, respectively. FⅦ-250 Phe was found in endoplasmic reticulum and Golgi apparatus, suggesting that the mutant FⅦ-250 Phe could be normally synthesized in the cells but was inefficiently secreted.</p><p><b>CONCLUSION</b>Compound heterozygous mutations in F7 gene (g.15975G>A and g.16750C>T) may be responsible for the FⅦ deficiency in this patient. The novel FⅦ 250 Phe can be transported from endoplasmic reticulum to Golgi apparatus, but may be degraded or inefficient.</p>


Subject(s)
Adult , Animals , Cricetinae , Humans , Male , CHO Cells , Cricetulus , Enzyme-Linked Immunosorbent Assay , Factor VII , Genetics , Physiology , Factor VII Deficiency , Genetics , HEK293 Cells , Mutation, Missense
15.
Article in Korean | WPRIM | ID: wpr-68961

ABSTRACT

Factor VII deficiency is a rare congenital bleeding disorder characterized by episodes of spontaneous bleeding in severely affected individuals. It is rare intussusception due to submucosal hematoma in coagulation factor deficiency patient. We recently experienced an adult small bowel intussusception in a patient with factor VII deficiency. A 36-yr old female patient with coagulation factor VII deficiency who was referred to our hospital underwent emergency surgery for treatment of the small bowel intussusceptions. Emergency laparoscopy-assisted small bowel resection was performed for treatment of small bowel intussusception caused by submucosal hematoma. The patient was successfully treated with close laboratory monitoring and laparoscopy-assisted small bowel resection.


Subject(s)
Adult , Female , Humans , Blood Coagulation Factors , Emergencies , Factor VII , Factor VII Deficiency , Hematoma , Hemorrhage , Intussusception
16.
Chinese Journal of Pediatrics ; (12): 817-820, 2012.
Article in Chinese | WPRIM | ID: wpr-348530

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the gene mutation in two pedigrees of inherited coagulation factor VII (FVII) deficiency, and investigate the relationship between the genotype and phenotype.</p><p><b>METHOD</b>The coagulation function and coagulation factors activity of probands were detected for phenotype diagnosis, all exons and junctions of FVII gene from the family members' genomic DNA were amplified using polymerase chain reaction (PCR), and detected the gene mutation by direct sequencing. Mutations were confirmed by reverse sequencing.</p><p><b>RESULT</b>The prothrombin time (PT) of proband 1 was 265.2 s, FVII:C was 22% and the PT of proband 2 was > 120 s, FVII:C was 1%. Homozygous 17844G→A mutation in No. 8 exon of FVII gene was identified in the proband 1 resulting in Gly343Ser, and heterozygosity for the same mutations were confirmed in his parents and a sister. The proband 2 was compound heterozygous, one mutation was the same as the proband 1 but was a heterozygosity that can also found in his mother and brother; the other heterozygosity mutation was located on No. 8 exon 18055G→A that resulted in Gln413Arg which was inherited from his father.</p><p><b>CONCLUSION</b>No. 8 exon of FVII gene encodes catalytic domain. Mutation found in those domain could change the FVII catalytic domain spatial structure, affected FVII function and stability, and the sufferer of homozygote and compound heterozygous may have clinical bleeding tendency. Almost no clinical findings in simple heterozygotes, however, a few of heterozygotes could have a tendency of bleeding because of genetic polymorphism which would reduce the FVII:C.</p>


Subject(s)
Child, Preschool , Humans , Infant , Male , Blood Coagulation Disorders , Blood , Genetics , DNA Mutational Analysis , Factor VII , Genetics , Factor VII Deficiency , Blood , Genetics , Heterozygote , Homozygote , Molecular Sequence Data , Mutation , Pedigree , Polymerase Chain Reaction , Prothrombin Time
17.
Article in Chinese | WPRIM | ID: wpr-295470

ABSTRACT

<p><b>OBJECTIVE</b>To investigate potential mutations and clinical features of 9 unrelated patients with inherited coagulation factor VII (FVII) deficiency.</p><p><b>METHODS</b>Clinical diagnosis was validated by assaying of coagulation parameters including prothrombin time, activated partial thromboplastin time, FVII activity and specific antigens. All exons, exon-intron boundaries, and 5' and 3' untranslated regions of F7 genes were amplified with PCR. Potential mutations were detected by direct sequencing of purified PCR products. Suspected mutations were confirmed by sequencing of the opposite strand.</p><p><b>RESULTS</b>All probands have featured prolonged prothrombin time, with FVII activity ranging between 2.0% to 6.0%. The titers of FVII antigen were significantly reduced in 7 probands. Eight mutations, including 6 missense mutations, 1 deletion and 1 insertion, were identified, among which 3 (Gln100Leu, Ser269Pro and g.11520_11521insT) were not described previously. Six mutations have located in the protease domain. All mutations were inherited, and consanguineous marriages were reported in 5 families. Mutations g.27_28delCT, Cys329Gly, Arg304Trp and His348Gln have been identified in unrelated families. There was a lack of correlation between the mutations and their clinical features. Two individuals with homozygous His348Gln mutations and 1 individual with homozygous Arg304Trp mutation were only mildly affected or asymptomatic. Two patients, who have respectively carried homozygous and heterozygous deletions of g.27_28delCT, were moderately affected and asymptomatic. In 4 patients carrying double heterozygous mutations, 1 (Ser269Pro and Cys329Gly) was asymptomatic, 2 (Arg304Trp and Cys329Gly, Arg277Cys and g.11520_11521insT, respectively) had a mild bleeding tendency, whilst 1 (Gln100Leu and His348Gln) has a moderate bleeding diathesis.</p><p><b>CONCLUSION</b>There seem to be hotspots of F7 gene mutations in ethnic Han Chinese populations. And there is a lack of correlation between particular types of mutations and clinical phenotypes.</p>


Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Base Sequence , Blood Coagulation Disorders, Inherited , Genetics , Factor VII , Genetics , Factor VII Deficiency , Genetics , Heterozygote , Homozygote , Molecular Sequence Data , Mutation
18.
PAFMJ-Pakistan Armed Forces Medical Journal. 2011; 61 (3): 387-390
in English | IMEMR | ID: emr-122844

ABSTRACT

To determine the frequency of bleeding disorders diagnosed at Armed Forces Institute of Pathology, Rawalpindi [AFIP Rwp]. Descriptive study. Department of Hematology, AFIP Rwp from January 2006 to June 2009. A total of 1836 patients of bleeding diathesis were included in the study. Hess test was done to investigate the vascular defects. Bleeding Time [BT] was done to screen platelet function defects. The 'clotting screen' and mixing studies were done to detect coagulation protein defects. Clot solubility test was performed to screen factor XIII deficiency. Out of 1836 patietns of bleeding diathesis 435 [23.7%] were diagnosed as having haemostatic defects. Out of these 435 patients 273 [62.8%] had coagulation factor deficiency, 81 [18.6%] had platelet function defects and 81 [18.6%] had vWF deficiency. Among the 273 coagulation factor deficiency patients, factor VIII deficiency was in 121 [44.3%], factor IX deficiency in 32 [11.7%], factor V deficiency in 18 [6.6%], factor XIII deficiency in 15 [5.5%], factor VII deficiency in 12 [4.4%], factor X deficiency in 9 [3.3%], factor I deficiency in 8 [2.9%] and factor II deficiency was in 3 [1.1%]. Multiple factor deficiency was 55 [20.1%]. No defects of vasculature were identified. Coagulation factor deficiencies, with factor VII deficiency being the commonest are the most frequent bleeding disorders. Platelet function defects and vWF deficiency also comprise significant proportion of the bleeding disorders


Subject(s)
Humans , Male , Female , Capillary Fragility , Bleeding Time , Clot Retraction , Factor V Deficiency , Factor VII Deficiency , Factor X Deficiency , Factor XI Deficiency , Factor XII Deficiency , Factor XIII Deficiency , von Willebrand Diseases
19.
Article in Chinese | WPRIM | ID: wpr-234328

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the gene mutation and the molecular pathogenesis of an inherited coagulation factor VII (F VII) deficiency pedigree with consanguineous marriage.</p><p><b>METHODS</b>The diagnosis was validated by coagulant parameter assay on the prothrombin time (PT), activated partial thromboplastin time, fibrinogen and coagulation factor activity. F VII gene mutations were analyzed in the proband and other family members by direct DNA sequencing of the PCR products of all exons, exon-intron boundaries and 5'and 3' untranslated sequences. The mutations were confirmed by reverse sequencing.</p><p><b>RESULTS</b>The values of PT and F VII activity in the proband were significantly abnormal, they were 30.9 s and 3% respectively. The PT of her daughter, father and mother was slightly extended to 21.2 s, 16.3 s and 16.1 s respectively, and the F VII activity was reduced to 22%, 25% and 35% respectively. The coagulant parameters of her younger brother were within normal range. Homozygous T-->G transition at position 11482 in exon 8 was identified in the proband resulting in His348Gln, and heterozygosity for His348Gln was confirmed in her daughter and her parents, and the normal wild-type was observed in her younger brother.</p><p><b>CONCLUSION</b>Homozygous missense mutation of His348Gln was found in a pedigree of hereditary F VII deficiency. The mutation was inherited from her heterozygote parents.</p>


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Infant, Newborn , Male , Middle Aged , Factor VII , Genetics , Factor VII Deficiency , Genetics , Homozygote , Mutation, Missense , Pedigree
20.
Chinese Journal of Hematology ; (12): 158-162, 2011.
Article in Chinese | WPRIM | ID: wpr-252005

ABSTRACT

<p><b>OBJECTIVE</b>To explore the mutations of coagulation factor VII (FVII) gene in one pedigree with hereditary FVII deficiency, and to investigate the molecular mechanisms of FVII deficiency.</p><p><b>METHODS</b>FVII gene mutations were analysed in the pedigree by direct DNA sequencing. The mutated DNA fragments were cloned into pMD19-T simple TA vector, and sequenced to confirm their distribution on chromosome. The plasma activity of FVII of the probands and their family members was detected with coagulation assay. The antigen of FVII were identified with ELISA.</p><p><b>RESULTS</b>Three gene mutations were detected in the pedigree: A/G to C at 15386 resulting in Arg353Pro/Gln353Pro, A to T at 15274 resulting in Lys316Stop, all three mutations were heterozygotes. Three kinds of polymorphisms were identified in his father: A to G transition at position 15386 resulting in Arg353Gln, heterozygotic deletion of 2050 - 2059 cctatatcct in promoter and G to A mutation in intron 1a, the same polymorphisms were found in his grandfather. The three polymorphisms were located in the same chromosome of his father.</p><p><b>CONCLUSION</b>Two mutations were found in the pedigree with hereditary FVII deficiency. One is nonsense mutation (Lys316Stop), the other is missense one (Gln353Pro). Gln353Pro and Lys316Stop might be the molecular mechanisms of FVII deficiency. The two novel mutations were reported for the first time in the literature.</p>


Subject(s)
Child, Preschool , Humans , Male , Base Sequence , DNA Mutational Analysis , Factor VII , Genetics , Factor VII Deficiency , Genetics , Heterozygote , Mutation, Missense , Pedigree , Polymorphism, Genetic , Sequence Deletion
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