Acute mesenteric thrombosis in a pregnant woman with Factor V Leiden mutation with a history of in vitro fertilization and embryo transfer: case report and literature review / Trombosis mesentérica aguda en gestante con mutación de Factor V Leiden y antecedentes de fertilización in vitro y transferencia de embriones: reporte de caso y revisión de la literature

Objectives: To report the case of a patient diagnosed with acute mesenteric vein thrombosis (AMVT) associated with Factor V Leiden mutation and a history of in vitro fertilization and embryo transfer and review the literature on risk factors and treatments performed for AMVT. Materials and methods: We reported the case of a 37-year-old pregnant woman. A bibliographic search was carried out in Medline/PubMed and LILACS, filtering by type of language (English and Spanish). Primary cohort studies, cases and controls, case reports and case series were included, which addressed the risk factors associated with the development of acute mesenteric thrombosis during pregnancy and treatments performed. Results: The search identified cases and control studies, case reports and case series related to mesenteric ischemia, pregnancy and in vitro fertilization. The literature reported that the main factors associated with mesenteric ischemia are pregnancy itself, genetic factors, drugs, protein C and protein S deficiency and idiopathic causes. Conclusions: SMV thrombosis is a life-threatening and very rarely seen condition that emerges in pregnancies. The literature suggests that, during gestation, the factors associated with the development of acute mesenteric thrombosis are hypercoagulability induced by pregnancy, the administration of oral estrogen during IVF-ET, and other precipitating factors. More studies are required to better understand the possible additional factors and build better optimal treatment algorithms.

Objetivos: presentar el caso de una paciente diagnosticada con trombosis aguda de la vena mesentérica (TAVM) asociada a mutación de Factor V Leiden y antecedente de fertilización in vitro y transferencia de embriones, y hacer una revisión de la literatura sobre los factores de riesgo y los tratamientos realizados en los casos de TAVM. Materiales y métodos: reporte de un caso de mujer gestante de 37 años. Se realizó una búsqueda bibliográfica en las bases de datos Medline/PubMed y LILACS, filtrando por idioma (inglés y español). Se incluyeron estudios de cohortes primarias, casos y controles, reportes de casos y series de casos que examinaran los factores de riesgo asociados con el desarrollo de trombosis mesentérica aguda durante el embarazo y los tratamientos realizados. Resultados: se identificaron estudios de casos y controles, reportes de casos y series relacionados con isquemia mesentérica, embarazo y fertilización in vitro, y se encontró que los principales factores asociados con isquemia mesentérica son el embarazo mismo, factores genéticos, medicamentos, la deficiencia de proteína C y S, y causas idiopáticas. Conclusiones: la trombosis de la vena mesentérica superior es una condición infrecuente que amenaza la vida y ocurre durante el embarazo. La literatura sugiere que, durante la gestación, los factores asociados con la trombosis mesentérica aguda son la hipercoagulabilidad inducida por el embarazo, la administración de estrógeno oral durante el proceso de fertilización in vitro y transferencia de embriones, y otros factores desencadenantes. Es necesario realizar más estudios para comprender mejor los posibles factores adicionales y desarrollar mejores algoritmos para un tratamiento óptimo.

Clinical phenotype and variantal analysis of a pedigree affected with hereditary coagulation factor V deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular basis for a pedigree affected with coagulation factor V (FV) deficiency.@*METHODS@#Clinical data of the patient and his family members was analyzed. Targeted capture and next-generation sequencing (NGS) and Sanger sequencing were carried out to detect potential variant of the FV gene.@*RESULTS@#The patient presented with jaundice and prolonged prothrombin time (PT) and activated partial thromboplastic time (APTT). V factor activity measured only 0.1% of the normal level, though the patient had no sign of bleeding. A paternal heterozygous variant c.653T>C (p.F218S) and a maternal heterozygous variant c.3642_3643del (p.P1215Rfs*175) were identified in the FV gene of the patient. His elder brother was a heterozygous carrier of the c.653T>C (p.F218S) variant. c.653T>C(p.F218S) was a known pathogenic variant, while the c.3642_3643del (p.P1215Rfs*175) variant was unreported previously.@*CONCLUSION@#Mutations of the FV gene probably underlie the hereditary coagulation factor V deficiency in this patient. NGS combined with Sanger sequencing has detected potential variant with efficiency and provided a reliable basis for clinical and prenatal diagnosis for this family.

Identification of a novel variant of F5 gene in a consanguineous pedigree affected with inherited coagulation factor V deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a consanguineous pedigree affected with inherited coagulation factor V deficiency.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from the pedigree and subjected to next generation sequencing for screening variants of the F5 gene. Suspected pathogenic variant was verified by using Sanger sequencing. Pathogenicity of the variant was evaluated according to ACMG guidelines.@*RESULTS@#A homozygous frameshifting variant, c.4096delC (p.Leu1366Phefs*3), was identified in the F5 gene in the proband, which was confirmed to be derived from her consanguineous parents. This variant was absent in all databases including 10 000 in-house Chinese exome sequences. Based on the ACMG guidelines, the c.4096delC was predicted to be a pathogenic variant.@*CONCLUSION@#A novel pathogenic variant has been identified in the F5 gene in a consanguineous pedigree with inherited coagulation factor V deficiency, which has enriched the spectrum of F5 gene variants.

Phenotypic and genetic analysis of a pedigree affected with hereditary FV deficiency due to a novel deletional variant of F5 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the phenotype and F5 gene variant in a pedigree affected with hereditary coagulation factor V (FV) deficiency.@*METHODS@#All of the exons, flanking sequences, and 5' and 3' untranslated regions of the F5 gene were subjected to PCR and direct sequencing. Suspected variant sites were confirmed by clone sequencing. Influence of the variants was predicted by using software including ClustalX and Mutation Taster.@*RESULTS@#The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were prolonged to 20.3 s and 59.2 s, respectively, while FV activity (FV:C) and FV antigen (FV:Ag) were reduced by 13% and 17%, respectively. The FV:C and FV:Ag of his father, sister and daughter were decreased to 35%, 37%, 29% and 42%, 46%, 35%, respectively. The proband was found to carry a heterozygous c.2851delT variant in exon 13 of the F5 gene, which caused a frameshift and resulted in a truncated protein (p.Ser923LeufsX8). In addition, a heterozygous c.1538G to A (p.Arg485Lys) variant was found in exon 10. The father, sister and daughter of the proband all carried the p.Ser923LeufsX8 variant, while his mother and son carried the heterozygous p.Arg485Lys polymorphism. His younger brother and wife were of the wild type. Bioinformatic analysis showed that p.Ser923 was highly conserved across various species. Mutation Taster scored 1.00 for the p.Ser923LeufsX8 variant, and the result has predicted a corresponding disease.@*CONCLUSION@#A heterozygous deletional mutation c.2851delT in exon 13 of the F5 gene and a heterozygous c.1538G to A polymorphism harbored by the proband may be associated with the decreased FV level in this pedigree.

Phenotypic and mutational analysis of a pedigree affected with hereditary coagulation factor Ⅴ deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the molecular pathogenesis for a pedigree affected with coagulation factor Ⅴ (FⅤ) deficiency.</p><p><b>METHODS</b>Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor Ⅱ activity (FⅡ: C), FⅤ activity (FⅤ: C), coagulation factor Ⅶ activity (FⅦ: C), and coagulation factor Ⅹ activity (FⅩ: C) were determined with a STAGO automatic coagulometer. FⅤ antigen (FⅤ: Ag) was detected with enzyme linked immunosorbent assay (ELISA). All exons and their flanking regions, and 5' and 3' untranslated regions of the F5 gene were analyzed by direct sequencing. Suspected mutation was verified by reverse sequencing as well as testing of family members. ClustalX software was used to analyze the conservative property of the mutation sites. PROVEAN and MutationTaster online software was used to predict the effect of the mutation on the protein function. Swiss-pdbViewer was used to analyze the protein model and interaction of amino acids.</p><p><b>RESULTS</b>The PT and APTT of the proband were slightly prolonged to 15.2 s and 41.8 s, respectively. And the FⅤ: C and FⅤ: Ag measured 55% and 62%, respectively. The FⅤ: C and FⅤ: Ag of his father and son were decreased to various extent (60%, 65% and 31%, 40%, respectively). A c.911G>A heterozygous mutation (Gly276Glu) was detected in exon 6 of the proband, for which her father and son were heterozygotes. The same mutation was not found in her mother, brother and husband. Conservation analysis showed that the Gly276 is highly conserved across various species. By bioinformatic analysis, the PROVEAN (scored -6.214) indicated Gly276Glu was harmful, and MutationTaster (scored 0.976) suggested that it is pathogenic. Model analysis suggested there are two hydrogen bonds between Gly276 and Ile298 in the wild type protein. When Gly276 was replaced by Glu276, the original hydrogen bond did not change, but the side chain of Glu was extended, which added steric hindrance with the surrounding amino acids, which resulted in decreased protein stability.</p><p><b>CONCLUSION</b>The heterozygous c.911G>A (Gly276Glu) mutation of the F5 gene probably underlies the decreased level of FⅤin the proband.</p>

A Case of Acquired Factor V Deficiency after Percutaneous Coronary Intervention / 대한내과학회지

Acquired factor V deficiency is extremely rare. Here we report the case of an 88-year-old female patient who presented with hematochezia 1 month after undergoing percutaneous coronary intervention. Her laboratory results showed an extremely prolonged prothrombin time and an activated partial thromboplastin time, but neither improved after fresh frozen plasma transfusion. She was finally diagnosed with acquired factor V deficiency and successfully treated with an immunosuppressant.

Genetic Confirmation of Congenital Factor V Deficiency in Korean Patients

No abstract available.

Factor V Deficiency in Korean Patients: Clinical and Laboratory Features, Treatment, and Outcome

Due to rarity of factor V (FV) deficiency, there have been only a few case reports in Korea. We retrospectively analysed the clinical-laboratory features of FV deficiency in 10 Korean patients. Between January 1987 and December 2013, 10 case reports published in a Korean journal or proceedings of Korea Society on Thrombosis and Hemostasis were reviewed. Severity is defined as mild (> 5% of factor activity), moderate (1%-5%), and severe (< 1%). The median age at diagnosis, six males and four females, was 26 years (range, 1 month-73 years). Six of 10 patients were classified as moderate, three as mild, and one as severe disease. Eight patients were diagnosed as inherited FV deficiency. The most frequent symptoms were mucosal tract bleedings (40%) such as epistaxis, and menorrhagia in female. Hemarthroses and postoperative bleeding occurred in one and four patients, respectively. Life-threatening bleeding episodes occurred in the peritoneal cavity (n = 2), central nerve system (n = 1), and retroperitoneal space (n = 1). No lethal haemorrhages happened to patients with mild disease. The majority of bleeding episodes were controlled with local measures and fresh-frozen plasma replacement. Two acquired FV deficient-patients showing life-threatening haemorrhages received the immunosuppressive therapy, but one of them died from postoperative bleeding complications. Despite the small sample size of this study due to rarity of the disease, we found that Korean patients with FV deficiency had similar clinical manifestations and treatment outcomes shown in previous studies.

Factor V Deficiency in Korean Patients: Clinical and Laboratory Features, Treatment, and Outcome

Due to rarity of factor V (FV) deficiency, there have been only a few case reports in Korea. We retrospectively analysed the clinical-laboratory features of FV deficiency in 10 Korean patients. Between January 1987 and December 2013, 10 case reports published in a Korean journal or proceedings of Korea Society on Thrombosis and Hemostasis were reviewed. Severity is defined as mild (> 5% of factor activity), moderate (1%-5%), and severe (< 1%). The median age at diagnosis, six males and four females, was 26 years (range, 1 month-73 years). Six of 10 patients were classified as moderate, three as mild, and one as severe disease. Eight patients were diagnosed as inherited FV deficiency. The most frequent symptoms were mucosal tract bleedings (40%) such as epistaxis, and menorrhagia in female. Hemarthroses and postoperative bleeding occurred in one and four patients, respectively. Life-threatening bleeding episodes occurred in the peritoneal cavity (n = 2), central nerve system (n = 1), and retroperitoneal space (n = 1). No lethal haemorrhages happened to patients with mild disease. The majority of bleeding episodes were controlled with local measures and fresh-frozen plasma replacement. Two acquired FV deficient-patients showing life-threatening haemorrhages received the immunosuppressive therapy, but one of them died from postoperative bleeding complications. Despite the small sample size of this study due to rarity of the disease, we found that Korean patients with FV deficiency had similar clinical manifestations and treatment outcomes shown in previous studies.

Antibiotic-Induced Acquired Factor V Inhibitor / 대한내과학회지

Acquired factor V inhibitor is a rare condition with a variety of clinical manifestations that range from no bleeding symptoms to life-threatening hemorrhage or thromboembolic events. Treatment is determined by the clinical course and focuses on controlling the hemorrhagic event and decreasing the antibody titer if bleeding symptoms are present. We report herein a case involving a 70-year-old man who developed acquired factor V inhibitor after antibiotic administration (11-day course of ceftriaxone and successive 5-day course of piperacillin-tazobactam) for pneumonia. His condition was characterized by elevated prothrombin and activated partial thromboplastin times without bleeding events. Coagulation factor assays revealed undetectable factor V activity and a factor V inhibitor level of 3.29 Bethesda units. After cessation of the antibiotics, both the prothrombin and activated partial thromboplastin times gradually normalized.

Analysis of a consanguineous pedigree featuring hereditary coagulation factor Ⅴ deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen potential mutation and explore the underlying mechanism for a consanguineous pedigree featuring hereditary coagulation factor Ⅴ (FⅤ) deficiency.</p><p><b>METHODS</b>Clinical diagnosis was validated by coagulant parameter assays of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), FⅤ procoagulant activity (FⅤ:C) and FⅤ antigen (FⅤ:Ag). Potential mutations of the F5 gene in the proband and his family members were analyzed by direct DNA sequencing of PCR products of all exons, exon-intron boundaries and 3', 5' untranslated regions. Suspected mutation was confirmed by reverse sequencing.</p><p><b>RESULTS</b>The PT and APTT in the proband were significantly prolonged, which measured 23.5 s (reference range 11.8-14.8 s) and 50.5 s (reference range 27.0-41.0 s), respectively. FⅤ activity and FⅤ antigen of the proband were significantly reduced to 8% and <1%, respectively. PT and APTT in the younger sister of the proband were also significantly prolonged (24.1 s and 62.4 s, respectively). Her FⅤ activity and FⅤ antigen were also significantly decreased (7% and <1%, respectively). PT and APTT of other family members were within the normal range. The homozygous missence mutation causing T→C transition at position 29170 in exon 5 of F5 gene has resulted in a Phe190Ser substitution in the proband. His younger sister was also homozygous for Phe190Ser. Heterozygosity for Phe190Ser was confirmed in his elder brother, elder sister, two daughters and niece, and their FⅤ activity were slightly decreased (57%, 73%, 72%, 66% and 75%, respectively). A normal wild type was observed in two younger brothers of the proband, and their FⅤ activity and FⅤ antigen were in the normal range.</p><p><b>CONCLUSION</b>Homozygous missence mutation of Phe190Ser has been found in above family featuring hereditary FⅤ deficiency. The homozygous missence mutation was inherited from the parents by consanguineous marriage. Phe190Ser probably underlies may underlie the pathogenesis of hereditary FⅤ deficiency in this pedigree.</p>

A Case of Acquired Factor V Deficiency Treated with Corticosteroids and Cyclophosphamide / 대한내과학회지

Acquired factor V deficiency is a rare bleeding disorder, the severity of which ranges from mild to fatal. There are various suggested treatments, including transfusion of fresh frozen plasma (FFP) or platelets, plasmapheresis and immunosuppressive therapy. We encountered a case of idiopathic acquired factor V deficiency with fatal retroperitoneal bleeding treated with steroid and cyclophosphamide.

A Case of Acquired Factor V Deficiency Treated with Corticosteroids and Cyclophosphamide / 대한내과학회지

Acquired factor V deficiency is a rare bleeding disorder, the severity of which ranges from mild to fatal. There are various suggested treatments, including transfusion of fresh frozen plasma (FFP) or platelets, plasmapheresis and immunosuppressive therapy. We encountered a case of idiopathic acquired factor V deficiency with fatal retroperitoneal bleeding treated with steroid and cyclophosphamide.

Frequency of bleeding disorders diagnosed at armed forces institute of pathology Rawalpindi

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

Prenatal diagnosis for two families of congenital factor V deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To provide genetic consulting and prenatal diagnosis for two families with congenital factor V deficiency based on the known mutations of factor V gene (G16088C and G69969T).</p><p><b>METHODS</b>Chorionic DNA was obtained at 12 weeks of gestation and analyzed to exclude maternal cell contamination through microsatellite DNA analysis. It was then amplified with PCR and sequenced to determine the presence of mutations in exons 3 and 23. Factor V activity of the blood was assayed at 22 weeks of gestation and 6 months after birth.</p><p><b>RESULTS</b>The fetus in case 1 was found to be a heterozygous carrier of the G16088C mutation, for whom factor V activity of the cord blood and peripheral blood were 15% and 53%, respectively. Fetus 2 did not carry the familiar G69969T mutation, for whom the factor V activity of cord blood and peripheral blood has measured 32% and 93%, respectively. Follow-up studies demonstrated that the two infants were both in good health without a tendency for bleeding.</p><p><b>CONCLUSION</b>In both cases, the genotypes were consistent with the phenotypes. This is the first report of prenatal diagnosis of congenital factor V deficiency.</p>

Analysis of phenotype and genotype in four Chinese pedigrees with inherited coagulation factor V deficiency / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify the phenotype and genotype in four Chinese pedigrees with inherited coagulation factor V (FV) deficiency.</p><p><b>METHODS</b>The tests of activated partial thromboplastin time (APTT), prothrombin time (PT), FV activity (FV:C) and FV antigen (FV:Ag) were used for phenotype diagnosis. All the exons and exon-intron boundaries of F5 gene were amplified by PCR and analyzed by direct sequencing.</p><p><b>RESULTS</b>The APTT and PT in each of the four probands were obviously prolonged, and both activity and antigen of FV in the four probands were extremely lower compared with that of normal mixed plasma. Sequencing of F5 gene in proband 1 identified a heterozygous mutation, G16088C (Asp68His), and four polymorphisms, T35788C (Met385Thr), A47295G (His1299Arg), A58668G (Met1736Val) and A74083G (Asp2194Gly), which were located in the same chromosome; proband 2 was homozygous for two mutations, C46253T (Arg952Cys) and C46724T(Gln1109stop); the F5 gene of proband 3 showed a homozygous missense mutation, C67793G(Pro2006Ala); and proband 4 was homozygous for one missense mutation, C74022T (Arg2174Cys).</p><p><b>CONCLUSION</b>Five mutations (Asp68His, Arg952Cys, Gln1109stop, Pro2006Ala and Arg2174Cys) and four polymorphisms (Met385Thr, His1299Arg, Met1736Val and Asp2194Gly) may lead to type I inherited FV deficiency for these four probands, respectively. Gln1109stop, Pro2006Ala and Arg2174Cys haven't been identified before.</p>

Combined deficiency of factors V and VIII caused by a novel compound heterozygous mutation of gene Lman1 / 中国实验血液学杂志

Combined deficiency of factor V and VIII (F5F8D) is a rare, autosomal recessive disorder caused by mutations of either lman1 or mcfd2. To identify mutations of these two genes in a Chinese F5F8D family, the samples of peripheral blood were collected from the proband and her parents. Coagulation tests were carried out, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg) and coagulate activity of FV, FVIII (FV:C, FVIII:C). The genomic DNA was extracted, then all the exons and intron/exon boundaries of these two genes were amplified by polymerase chain reaction (PCR). The products were finally analyzed by direct sequencing. The results showed that the proband's APTT, PT, TT, Fg, FV:C and FVIII:C were 82.2 sec, 19.6 sec, 18.6 sec, 2.9 g/L, 7.1% and 18.7% respectively, while those parameters of the parents were all within the normal range. Two pathogenic mutations were identified in lman1 gene of the proband: one was the heterozygous c.912_913insA in exon 8 resulting in a frameshift of p.Glu305fsX20; the other was the heterozygous c.1366C > T in exon 11 resulting in p.Arg456X. The proband's father and mother were heterozygous for c.1366C > T and c.912_913insA respectively. It is concluded that F5F8D of the proband is caused by a novel compound heterozygous mutation of the lman1 gene, which has never been reported.

Gene analysis of five inherited factor V deficiency cases / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify gene mutations involved in five cases of inherited factor V (FV) deficiency.</p><p><b>METHODS</b>Activity of FV was determined by one-stage clotting assay using FV-deficiency plasma, and FV antigen by an ELISA assay. All the exons and exon-intron boundaries of FV gene were amplified by PCR and then DNA sequencing. Restriction enzyme analysis was used to analyze the probands, their family members and healthy volunteers.</p><p><b>RESULTS</b>Both activity and antigen of FV in the 5 patients were extremely lower compared with that of normal mixed plasma. Six mutations were identified in these 5 patients, G69969T (G2079V), C45533T (R712Ter), C46796T (R1133Ter), G45366A (C656Y), C46253T (R952C) and G16088C (D68H), the latter three were novel mutations reported for the first time and the C46253T (R952C) was the first missense mutation reported in B domain. The result of sequencing or restriction enzyme analysis showed that the three novel missense mutations were not caused by single nucleotide polymorphisms.</p><p><b>CONCLUSION</b>Gene mutations in 5 type I inherited FV deficiency of patients including 2 nonsense mutations and 4 missense mutations identified which led to the instability of FV protein and the reducing of FV: Ag in the plasma.</p>

Identification of two novel mutations of human blood coagulation factor V gene in a Chinese family with congenital factor V deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To discover the mutations of human blood coagulation factor V (FV) gene in a Chinese family with congenital factor V deficiency, and to explore the molecular mechanism associated with the congenital factor V deficiency.</p><p><b>METHODS</b>PCR and DNA sequencing were used to look for the FV gene mutations in the proband. And the novel mutation were testified by PCR restriction fragment length polymorphism technique or reverse DNA sequencing. One hundred healthy volunteers were chosen as controls at random.</p><p><b>RESULTS</b>Two novel mutations were discovered in the FV gene of proband, which were the A1763C missense mutation in exon 11 and the splicing site mutation in the 3' terminal of intron 16 (G-->T). The pedigree analysis showed that the two mutations inherited from his parents respectively: the A1763C came from his father, and the G-->T from his mother. The A1763C missense mutation in exon 11 was not found in each of 100 healthy volunteers.</p><p><b>CONCLUSION</b>The congenital deficiency of FV in the proband might be caused by the A1763C missense mutation in exon 11 and the splicing site mutation in the 3' terminal of intron 16, which jointly caused the proband to be a double heterozygote.</p>