1/39. Intracranial haemorrhage due to factor v deficiency.factor v deficiency is a rare coagulation disorder which is inherited autosomal recessively. factor v deficiency should be considered in infants with bleeding disorders and prolonged prothrombin and activated partial thromboplastin times if bleeding continues in spite of vitamin k injection. In this article, the case of an infant with an intracranial haemorrhage due to congenital factor v deficiency is reported.- - - - - - - - - - ranking = 1keywords = coagulation disorder, coagulation (Clic here for more details about this article) |
2/39. Familial coagulation factor v deficiency caused by a novel 4 base pair insertion in the factor V gene: factor V Stanford.An index patient with pseudohomozygosity for factor V Leiden was identified. Each of his two children inherited a different paternal factor V allele; a daughter was heterozygous for factor V Leiden, with 100% factor V activity, and a son was heterozygous for factor v deficiency, with 50% factor V activity. Genomic dna was obtained from family members, and the 25 factor V exons and flanking intronic regions were sequenced in the proband and confirmed in the children. Within exon 13 of factor V, a 4 base insertion was found at NT 2856 in the proband and son. but not the daughter. This mutation, here designated factor V Stanford, results in a frameshift with loss of a thrombin activation site (R1545V) and premature termination of translation at amino acid 1560.- - - - - - - - - - ranking = 0.16397338458647keywords = coagulation (Clic here for more details about this article) |
3/39. Familial association of hypoplasminogenemia and heterozygous factor v deficiency.The coinheritance of hypoplasminogenemia and heterozygous factor v deficiency in a relative with thrombotic disease and no hemorrhagic tendency is described. The proposita, a 28-year-old woman, suffered from neurologic disturbances due to two ischemic cerebral lesions confirmed by nuclear magnetic resonance scan. She was found to be affected with heterozygous plasminogen deficiency in a coagulation study for inherited thrombophilia. Moreover, she disclosed a prolongation of prothrombin time and activated partial thromboplastin time, which was compatible with heterozygous factor v deficiency. Her father, with a history of deep vein thrombosis, was also affected with plasminogen deficiency, as well as three brothers and one sister who were asymptomatic. The mother of the proposita showed borderline or slightly decreased factor V levels and normal plasminogen levels; she was therefore considered to be heterozygous for factor v deficiency. Heterozygous factor v deficiency was also found in one brother and one sister of the proposita, and they were both asymptomatic. Among the other available family members, one brother and one sister of the proposita, all asymptomatic for either thrombotic or bleeding events, showed a normal clotting and fibrinolytic profile. To our knowledge, this is the first case of combined heterozygous plasminogen and factor v deficiency in the same family. Two of six patients with hypoplasminogenemia showed thrombotic events, and in one of these symptomatic cases the coexistence of factor v deficiency did not prevent the occurrence of thrombosis. As expected, no hemorrhagic tendency was observed in patients with heterozygous factor v deficiency, who may be mildly symptomatic only in 10% of cases.- - - - - - - - - - ranking = 0.040993346146618keywords = coagulation (Clic here for more details about this article) |
4/39. A novel two base pair deletion in the factor V gene associated with severe factor v deficiency.We studied a family in which the proband, a 13-year-old boy, had unmeasurable plasma levels of coagulation factor V antigen and activity. Clinical symptoms were severe, with several episodes of haemorrhages in the mucosal tracts (gastrointestinal, nose and urinary) and recurrent haemarthroses that caused permanent arthropathy. sequence analysis of the factor V gene demonstrated the presence of a novel 2 base pair (bp) homozygous deletion in exon 13 at positions 2833-2834. This mutation, present in the heterozygous state in the asymptomatic mother and absent in the healthy brother, introduced a frameshift and a premature stop at codon 900. This would predict the synthesis of a truncated factor V molecule, lacking part of the B domain and the complete light chain. Because of the existence of a surveillance mechanism that selectively recognizes and degrades mRNA molecules carrying premature termination codons, we analysed the relative abundance of mutant vs. wild-type mRNA molecules in the platelets of the heterozygous proband's mother. The mutant mRNA was significantly reduced in amount (mutant/wild-type ratio 0.35). This is the first reported mutation in the factor V gene causing severe factor v deficiency, the effect of which was quantitatively analysed at mRNA level.- - - - - - - - - - ranking = 0.040993346146618keywords = coagulation (Clic here for more details about this article) |
5/39. A missense mutation (Y1702C) in the coagulation factor V gene is a frequent cause of factor v deficiency in the Italian population.BACKGROUND AND OBJECTIVES: Factor V (FV) deficiency is a rare bleeding disorder whose molecular bases are poorly characterized. We have recently described a FV missense mutation (Y1702C) predicting reduced FV levels in a thrombophilic patient and in a healthy individual. The aim of the present work was to assess the prevalence of the FV Y1702C mutation among subjects with FV deficiency. DESIGN AND methods: Carriership of the FV Y1702C mutation was tested in 8 patients with severe FV deficiency (FV:C <8%), in 16 individuals with asymptomatic partial FV deficiency (mean FV:C 38.0%, SD 11.6%) and in 9 patients with pseudo-homozygous APC-resistance (mean FV:C 46.2%, SD 3.6%). An AccI-restriction protocol was employed for rapid mutation screening. RESULTS: The FV Y1702C mutation was detected in two unrelated patients with unmeasurable FV levels (one being homozygous and the other doubly heterozygous for a still unknown mutation) and in one subject with partial FV deficiency (FV:C 30%). A striking difference in bleeding phenotype was observed between the homozygous patient and her asymptomatic brother with the same FV genotype. A multi-point FV haplotype analysis was performed in all unrelated carriers of the FV Y1702C mutation. Three haplotypes were found to underlie the mutation in different individuals, suggesting that it might have arisen independently more than once. INTERPRETATION AND CONCLUSIONS: FV Y1702C is a common cause of FV deficiency in the Italian population and might be a recurrent mutation.- - - - - - - - - - ranking = 0.16397338458647keywords = coagulation (Clic here for more details about this article) |
6/39. Five novel mutations in the gene for human blood coagulation factor V associated with type I factor v deficiency.Coagulation factor V (FV) plays an important role in maintaining the hemostatic balance in both the formation of thrombin in the procoagulant pathway as well as in the protein c anticoagulant pathway. FV deficiency is a rare bleeding disorder with variable phenotypic expression. Little is known about the molecular basis underlying this disease. This study identified 5 novel mutations associated with FV deficiency in 3 patients with severe FV deficiency but different clinical expression and 2 unaffected carriers. Four mutations led to a premature termination codon either by a nonsense mutation (single-letter amino acid codes): A1102T, K310Term. (FV Amersfoort) and C2491T, Q773Term. (FV Casablanca) or a frameshift: an 8-base pair deletion between nucleotides 1130 and 1139 (FV Seoul(1)) and a 1-base pair deletion between nucleotides 4291 and 4294 (FV Utrecht). One mutation was a novel missense mutation: T1927C, C585R (FV Nijkerk), resulting in the absence of mutant protein despite normal transcription to rna. Most likely, an arginine at this position disrupts the hydrophobic interior of the FV A2 domain. The sixth detected mutation was a previously reported missense mutation: A5279G, Y1702C (FV Seoul(2)). In all cases, the presence of the mutation was associated with type I FV deficiency. Identifying the molecular basis of mutations underlying this rare coagulation disorder will help to obtain more insight into the mechanisms involved in the variable clinical phenotype of patients with FV deficiency.- - - - - - - - - - ranking = 4.0983947943917keywords = coagulation disorder, blood coagulation, coagulation (Clic here for more details about this article) |
7/39. Coexistence of a novel homozygous nonsense mutation in exon 13 of the factor V gene with the homozygous Leiden mutation in two unrelated patients with severe factor v deficiency.A novel homozygous 3571C-->T nonsense mutation predicting the synthesis of a truncated factor V (FV) molecule was identified in exon 13 of the human coagulation factor V gene in two unrelated Italian probands with undetectable plasma levels of FV antigen and activity. Both patients were also homozygous for the FV Leiden mutation. reverse transcription polymerase chain reaction studies showed strongly reduced mRNA levels of the mutant FV allele and FV heavy and light chains were not measurable in the plasma of the probands and reverse transcriptase. Haplotype analysis indicated that the nonsense mutation in both families had a common founder a long time ago.- - - - - - - - - - ranking = 0.040993346146618keywords = coagulation (Clic here for more details about this article) |
8/39. Late presentation of congenital factor v deficiency--a case report.Congenital factor deficiency is a rare coagulation disorder, which is inherited in an autosomal recessive manner. The severity of bleeding symptoms in general is only partially related to the degree of factor v deficiency in plasma. In this report, a boy presenting with hemarthrosis in his late adolescence due to congenital factor v deficiency is reported.- - - - - - - - - - ranking = 1keywords = coagulation disorder, coagulation (Clic here for more details about this article) |
9/39. Severe coagulation factor v deficiency caused by 2 novel frameshift mutations: 2952delT in exon 13 and 5493insG in exon 16 of factor 5 gene.A male infant with severe bleeding tendency had undetectable factor V activity. sequence analysis of the proband's dna revealed one base deletion in exon 13 (2952delT) and one base insertion in exon 16 (5493insG) in heterozygous form. Both mutations introduced a frameshift and a premature stop at codons 930 and 1776, respectively. The proband's father and mother were heterozygous for 2952delT and for 5493insG, respectively. Both mutations would result in the synthesis of truncated proteins lacking complete light chain or its C-terminal part. In the patient's plasma, no factor V light chain was detected by enzyme-linked immunosorbent assay. The N-terminal portion of factor V containing the heavy chain, and the connecting B domain was severely reduced but detectable (1.7%). A small amount of truncated factor V-specific protein with a molecular weight ratio of 236 kd could be immunoprecipitated from the plasma and detected by Western blotting. This protein, factor V(Debrecen), corresponds to the translated product of exon 16 mutant allele.- - - - - - - - - - ranking = 0.16397338458647keywords = coagulation (Clic here for more details about this article) |
10/39. Factor V inhibitor in neonatal intracranial hemorrhage secondary to severe congenital factor v deficiency.We report a newborn infant girl, born to consanguineous parents, with recurrent intracranial hemorrhage secondary to congenital factor v deficiency with factor V inhibitor. Repeated transfusions of fresh-frozen plasma (FFP) and platelet concentrates, administrations of immunosuppressive therapy (prednisolone and cyclophosphamide), and intravenous immunoglobulin failed to normalize the coagulation profiles. Exchange transfusion followed-up by administrations of activated prothrombin complex and transfusions of FFP and platelet concentrates caused a temporary normalization of coagulation profile, enabling an insertion of ventriculoperitoneal (VP) shunt for progressive hydrocephalus. The treatment was complicated by thrombosis of left brachial artery and ischemia of left middle finger. The child finally died from another episode of intracranial hemorrhage 10 days after insertion of the VP shunt.- - - - - - - - - - ranking = 0.081986692293236keywords = coagulation (Clic here for more details about this article) |
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