Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the enzymes phospholipases C and D on Factor VIII were investigated. Phospholipase D was found to activate the partially purified intact Factor-VIII molecule maximally at a final concentration of 0.6 U/ml. Neither the dissociated small molecular weight component nor the high molecular weight component were activated. Phospholipase C, on the other hand, inactivated both the intact and the dissociated Factor-VIII molecule. Phospholipase D, however, had no effect on the haemophilic cryoprecipitate or the partially purified haemophilic Factor VIII. The implications of these results for the genetic control of the Factor-VIII molecule are discussed. In this connection, haemophilia A is hypothesized to be caused by an X-linked enzyme effect that impairs phospholipid assembly of the Factor-VIII protein, whereas von Willebrand's disease might be due to a structural defect of the Factor-VIII protein.
 ...
PMID:Effect of phospholipases on factor-VIII activity. 30 30

A Northern Ireland family is reported on, in which there is X-linked inheritance of clinical anophthalmos. Multi-point linkage analysis suggests that the gene is localized to the Xq27-28 region (Z = 1.9, Theta = 0.08), though not between the DNA markers DX13 and Factor VIII.
 ...
PMID:X-linked clinical anophthalmos. Localization of the gene to Xq27-Xq28. 167 29

A large survey of hemophilia A carried out with almost complete ascertainment on the island of Sardinia suggests that the variation of plasma levels of Factor VIII coagulant activity in normal individuals is largely controlled by a series of normal isoalleles or by closely linked modifiers. This variation is expected to affect the laboratory detection of the hemophilia A (HA) heterozygotes in addition to the X-inactivation-dependent mosaicism and the type of deficient mutant present in a given pedigree. The Sardinian pedigrees yielded 13 new cases of nonrecombinants between the loci for HA and glucose-6-phosphate dehydrogenase (G6PD), as well as four nonrecombinants between HA and Deutan color blindness. These findings bring to a total of 58 the number of scorable sibs and nonrecombinants thus far known for the linkage HA-G6PD. From such a figure it has been possible to infer that the 90% upper limit of meiotic recombination between the two loci is below 4%, thus justifying the application of the "linkage diagnostic test" for the detection of HA heterozygotes and the prenatal diagnosis of the hemophilic fetuses in families that segregate at both loci. In three out of the five HA pedigrees of our series that segregate also for G6PD or Deutan color blindness, the observed segregation of the combined phenotypes can be best explained by assuming the occurrence of a fresh mutation in the maternal grandfathers. Such a finding points out the opportunity to reevaluate Haldane's hypothesis of a possible higher incidence of X-linked mutations in the human male. It is anticipated that each of the issues addressed by the present study will be amenable to experimental verification as soon as suitable molecular probes become available to screen for common multiallelic DNA polymorphisms in the subtelomeric region of the X-chromosome long arm.
 ...
PMID:Studies on hemophilia A in Sardinia bearing on the problems of multiple allelism, carrier detection, and differential mutation rate in the two sexes. 642 Nov 51

A review is given of the history and distribution of hemophilia in dogs. The current knowledge of Factor VIII relative to hemophilia A and von Willebrand's Disease is presented. The tests required for distinguishing between hemophilia A, hemophilia B, von Willebrand's Disease, and various disorders caused by other factor defects in the coagulation cascade are described. X-linked, recessive inheritance of hemophilia A is illustrated in genealogical diagrams. The precautions required in connection with blood sampling for diagnostic tests are emphasized.
 ...
PMID:Hemophilia in dogs, with special reference to hemophilia A among German shepherd dogs in Denmark. I: Pathophysiology, laboratory tests and genetics. 643 87

Factor VIII is a trace plasma glycoprotein involved as a cofactor in the activation of factor X by factor IXa. Inherited deficiency of factor VIII results in the X-linked bleeding disorder hemophilia A which has been documented in humans, horses, sheep and dogs. In this report, the putative proximal promoter, 5' untranslated region, complete coding sequence and 3' untranslated region of the canine factor VIII gene have been characterized. When compared to the human gene, the 5' flanking region shows conservation of transcription factor binding sites in the 5' untranslated region. Alignment of the amino acid sequence with that of the previously reported human, mouse and pig proteins demonstrates sequence identity of between 77 and 92% for the A1, A2, A3, C1 and C2 domains but an identity of only between 44 and 62% for the central B domain. The three thrombin cleavage sites are conserved in the canine sequence as are the protein C cleavage sites and the von Willebrand factor binding region. In addition, all six tyrosine residues that are known to undergo sulfation in the human protein are conserved in the dog. The 3' untranslated region of the canine gene extends 1.5 kilobases. The initial 700 basepairs of this sequence are highly GC rich and the sequence terminates with 2 alternative potential polyadenylation sites. The knowledge of this sequence, in combination with a well described canine model of hemophilia A, provides the necessary starting point for studies addressing the long-term evaluation of factor VIII gene therapy using a homologous transgene.
 ...
PMID:The canine factor VIII cDNA and 5' flanking sequence. 949 83

Hemophilia A and B are X-linked genetic disorders caused by deficiency of the coagulation factors VIII and IX, respectively. Because of the health hazards and costs of current product replacement therapy, much effort is devoted to the development of gene therapy for these disorders. Approaches to gene therapy for the hemophilias include: ex vivo gene therapy in which cells from the intended recipients are explanted, genetically modified to secrete Factor VIII or IX, and reimplanted into the donor; in vivo gene therapy in which Factor VIII or IX encoding vectors are directly injected into the recipient; and non-autologous gene therapy in which universal cell lines engineered to secrete Factor VIII or IX are enclosed in immuno-protective devices before implantation into recipients. Research into these approaches is aided by the many murine and canine models available. While problems of achieving high and sustained levels of factor delivery, and issues related to efficacy, safety and cost are still to be resolved, progress in gene therapy for the hemophilias has been encouraging and is likely to reach human clinical trial in the foreseeable future.
 ...
PMID:Gene therapy for hemophilia. 1067 74

Short interspersed elements, such as Alu elements, have propagated to more than one million copies in the human genome. They affect the genome in several ways, caused by retrotransposition, recombination between elements, gene conversion, and alterations in gene expression. These events, including novel insertions into active genes, have been associated with a number of human disorders. Hemophilia A is an X-linked severe bleeding disorder and is caused by mutations in the Factor VIII gene. The spectrum of mutations includes point mutations, rearrangements, insertions, and deletions. Recently, an Alu retrotransposition event in a coding exon has been reported in a family with a severe form of hemophilia A. This was the first report of an Alu insertion in the Factor VIII gene. Here, we report a second Alu insertion event that lies in an intron of the same gene that causes exon skipping and the complete disruption of gene expression.
 ...
PMID:Exon skipping caused by an intronic insertion of a young Alu Yb9 element leads to severe hemophilia A. 1288 4

Haemophilia A and B are X-linked disorders resulting from deficiency of Factor VIII and IX, respectively. Clinical sequellae of Factor VIII or IX deficiency include spontaneous and traumatic haemorrhages into joints, soft tissues, and muscles. The cornerstone of therapy has been replacement of the deficient factor, historically with pooled-plasma derivatives. The unfortunate blood-borne infection transmission (such as HIV, hepatitis B and C viruses), inhibitor formation, immunosuppression, and, in certain cases, thrombosis by these products has spawned major advances and innovations in the manufacture of clotting products. Recombinant technology has virtually eliminated transmissible disease risk; yet, the presence of albumin in second and third generation recombinant products raises, at the least, theoretical risk of prions and parvovirus B19. Other non-infectious complications, including inhibitor formation, allergic reactions, and thrombosis, remain formidable concerns. Despite this, recombinant factors remain the most attractive treatment approach for haemophilia. Future improvement awaits the development of safe and effective gene transfer technology.
 ...
PMID:Safety of the new generation recombinant factor concentrates. 1290 37

Hemophilia A is an X-linked bleeding disorder caused by defective coagulation Factor VIII (FVIII). Although the efficacies of existing treatment using purified or recombinant FVIII are good, there remain shortcomings in using this particular form of treatment. A few FVIII gene therapy clinical trials have been initiated with modest improvements recorded, but these are no longer being continued due to insufficient efficacy. However, with the progress in the development of gene delivery vectors and the availability of mouse and canine hemophilia A models, gene therapy of hemophilia A remains an area of hot pursuit.
 ...
PMID:Gene therapy for hemophilia A. 1723 42

Haemophilia A (HA) and B (HB) are X-linked congenital disorders caused by deficiencies of Factor VIII and FIX. Being the world's most populous country, China potentially has a large population of haemophilia patients. During the last decade, no studies have been published regarding the clinical information of haemophilia in China. A retrospective study was conducted in patients with HA and HB referred to Tianjin Haemophilia Centre between 2002 and 2012. We identified 1,226 males with haemophilia (1,019 HA and 207 HB). The results revealed that activate partial thromboplastin time was negatively correlated plasma factor level of person with haemophilia. Our data did not offer sufficient evidence of any relationship existed between disease severity and risk or site of haemorrhage. There was a trend toward a higher inhibitor incidence induced by plasma-derived factor VIII products, than by recombinant FVIII (rFVIII) alone. It seemed that second generation of rFVIII more likely developed inhibitor, and first generation of rFVIII was nevertheless more closely connected to high-titer inhibitor. We found that delay in diagnosis and blood-borne infections were significantly reduced, while the joint deformity rate did not decrease despite the wide variety of products to choose from in this decade. The development of inhibitor still remains a major challenge in replacement therapy in haemophilia.
...
PMID:Retrospective analysis of 1,226 Chinese patients with haemophilia in a single medical centre. 2419 52


1 2 Next >>