Clinical, biological, and genetic features in an afibrinogenemia patient series in Algeria.

Introduction: The incidence of afibrinogenemia had not been previously reported in Algeria. Afibrinogenemia patients are prone to both haemorrhagic and thrombotic complications. Predictive markers of thrombosis in afibrinogenemia patients are not existent.

Lethal factor VII deficiency due to novel mutations in the F7 promoter: functional analysis reveals disruption of HNF4 binding site.

Hereditary factor VII (FVII) deficiency is a rare autosomal recessive disorder. Deleterious mutations that prevent the synthesis of any amount of functional FVII have been associated with life-threatening haemorrhage in neonates. Here we report two infants, of Maghrebian origin, who suffered a fatal spontaneous cerebral haemorrhage.

Characterization of a homozygous Gly11Val mutation in the Gla domain of coagulation factor X.

Factor (F) X deficiency is a rare inherited autosomal recessive trait. We report on a patient affected by a severe bleeding diathesis. Mutations were sought by F10 sequence analysis.

A two adenine insertion polymorphism in the 3' untranslated region of factor VII gene is associated with peripheral arterial disease but not with venous thrombosis. Results of case-control studies.

Polymorphic variants of genes encoding blood coagulation proteins have been extensively studied as risk factors for venous or arterial thrombosis A variation in the 3' untranslated region (UTR) involved in the post-transcriptional regulation of factor VII (FVII) gene has been recently identified, a two adenine insertion/deletion at nucleotide 11293. In this study, we investigated its effect on the risk of thrombosis in the frame of two case-control studies, including patients suffering from peripheral arterial disease (PAD) or venous thromboembolic (VTE) disease. The 3'UTR FVII gene polymorphism was investigated i) in 181 patients who had symptomatic atherosclerotic disease of the lower limbs, ii) in 178 patients who had had at least one episode of objectively diagnosed deep venous thrombosis and iii) in controls matched for age and sex.

Recurrence of a Phe31Ser mutation in the Gla domain of blood coagulation factor X, in unrelated Algerian families: a founder effect?

The presence of gene lesions in blood coagulation factor X (FX) was investigated in eight FX-deficient patients with severe bleeding symptoms, originating from five unrelated Algerian families (FX coagulant activity <1%, FX antigen ranging from 2% to 16%). A missense mutation (p.Phe31Ser) in the Gla domain was found in homozygous form for all patients but one, who is a compound heterozygote for the Phe31Ser mutation and for a non-sense mutation, Tyr130Term in EGF-2 domain.

Effect of oversulfated dermatan sulfate derivatives on platelet aggregation.

We have investigated the effect on human platelet aggregation of native dermatan sulfate (DS) and three oversulfated DS derivatives with different sulfur contents, and compared it with that of unfractionated heparin. An inhibitory effect on collagen-induced platelet aggregation was observed only with unfractionated heparin at high concentrations, whereas no inhibitory effect was observed when arachidonic acid was used. Heparin was the most potent inhibitor of the thrombin-induced platelet aggregation in platelet-rich plasma (PRP), whereas the oversulfated DS had a higher potency than the native DS.

Oriented scanning is the leading mechanism underlying 5' splice site selection in mammals.

Splice site selection is a key element of pre-mRNA splicing. Although it is known to involve specific recognition of short consensus sequences by the splicing machinery, the mechanisms by which 5' splice sites are accurately identified remain controversial and incompletely resolved. The human F7 gene contains in its seventh intron (IVS7) a 37-bp VNTR minisatellite whose first element spans the exon7-IVS7 boundary.

Thrombin inhibition by antithrombin in the presence of oversulfated dermatan sulfates.

DSS1 and DSS2 are two oversulfated dermatan sulfate derivatives with sulfur contents of 7.8% and 11.5%, respectively.

Inherited factor VII deficiency: identification of two novel mutations (A191V and T239P) in the catalytic domain.

We describe here five F7 mutations found in four patients without bleeding history, despite constitutional coagulation Factor VII (FVII) deficiency. All five mutations are missense and affect the catalytic domain of FVII (A191T, A191V, T239P, R224Q and M298I). The A191V and T239P mutations are novel and were found in homozygous patients with no clinical bleeding tendency.

Factor VII gene intronic mutation in a lethal factor VII deficiency: effects on splice-site selection.

In a patient with lethal factor VII (FVII) deficiency, 2 homozygous nucleotide substitutions were identified in the F7 gene: a IVS7+2T>G transversion involving the IVS7 donor splice site, followed by a mutation at nucleotide 10588 that would result in a missense variation (Arg224Gln). The mutated splice site, located within the first repeat of a minisatellite, is followed by a variable number of pseudo-sites, normally silent. To investigate the consequences of this mutation on F7 splicing, we designed normal and mutant minigenes, spanning exons 5 to 8.

A fucosylated chondroitin sulfate from echinoderm modulates in vitro fibroblast growth factor 2-dependent angiogenesis.

Fucosylated chondroitin sulfate (FucCS), a glycosaminoglycan obtained from sea cucumber, has the same structure as mammalian chondroitin sulfate, but some of the glucuronic acid residues display sulfated fucose branches. This new polysaccharide has a more favorable effect than heparin on vascular cell growth. It inhibits smooth muscle cell proliferation as heparin, and it has a potent enhancing effect on endothelial cell proliferation and migration in the presence of heparin-binding growth factors.

Characterization of two novel splice site mutations in human factor VII gene causing severe plasma factor VII deficiency and bleeding diathesis.

The molecular basis of severe type I factor (F)VII deficiency was investigated in two Algerian patients. One patient, a 13-year-old-girl who has suffered from severe bleeding since birth, was homozygous for a 7-bp deletion (nt 7774-7780) and a 251-bp insertion (nt 7773-7781) of mitochondrial origin, in IVS 4 acceptor splice site. The other patient, an infant who died from massive intracranial haemorrhage, was homozygous for a transversion in the IVS 7 donor splice site (T9726+2-->G) and a missense mutation in exon 8 (G10588-->A; Arg224-->Gln).