Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII

Bernardi, Francesco; Liney, D.; Patracchini, P.; Gemmati, Donato; Legnani, Cristina; Arcieri, P.; Pinotti, Mirko; Redaelli, R; Ballerini, Giorgio; Pemberton, S.; Wacey, A. I.; Mariani, Guglielmo; Tuddenham, Edward G. D.; Marchetti, Giovanna

doi:10.1111/j.1365-2141.1994.tb04793.x

Cited by 57 publications

(39 citation statements)

References 36 publications

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“…They revealed the additional presence of FVII deficiency with plasma FVII:C levels of less than 1% and normal levels of FVII:Ag (Table I). FVII mutational analysis identified in both probands the presence, in the homozygote state, of the previously reported missense mutation Cys310Phe [6,7].…”

Section: Case Reportmentioning

confidence: 63%

A rare inherited coagulation disorder: Combined homozygous factor VII and factor X deficiency

et al. 2004

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The combined presence in the homozygous state of more than one recessively transmitted coagulation defect may rarely occur in countries with a high rate of consanguinity. In an Iranian family consisting of two parents (second cousins) and two affected siblings, initial phenotypic analysis led to a diagnosis of mild FX deficiency (10-19% FX activity, 42-54% FX:Ag), and genotyping revealed a new homozygous missense mutation in the corresponding gene (Ser3Cys). As both of the sibs had a severe bleeding history that was not compatible with mild deficiency of FX, further phenotypic analysis revealed the additional presence of severe FVII deficiency (<1% FVII activity; 63-111% FVII:Ag) associated with the homozygous missense gene mutation Cys310Phe. In this kindred, lack of identification of the double coagulation defect might have led not only to incomplete understanding of the clinical phenotype but also to an incorrect prenatal diagnosis.

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Section: Case Reportmentioning

confidence: 63%

A rare inherited coagulation disorder: Combined homozygous factor VII and factor X deficiency

et al. 2004

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“…Six of these patients belonging to 5 different kindreds came from our personal files. The remaining 16 patients were obtained from the literature (tables 1, 2) [10,13,14,19,20,21,22,23,24,25]. …”

Section: Resultsmentioning

confidence: 99%

Ox Brain versus Rabbit Brain Thromboplastin Assays Are the Best Tool for a Preliminary Diagnosis of the Arg304Gln Factor VII Defect (FVII Padua)

et al. 2010

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Factor VII (FVII) deficiency, the most frequent defect among the rare bleeding disorders, is commonly divided into type I and type II. In the former, there is a concomitant decrease in FVII activity and antigen. In the latter, there is a clear discrepancy between activity which is low and antigen which is normal or nearly normal. FVII Padua (Arg304Gln) is characterized by different reactivity towards different tissue thromboplastins. FVII levels were assayed by the use of different tissue thromboplastins, namely rabbit brain, human placenta, human recombinant and ox brain thromboplastin, in 6 homozygous patients. Cases reported in the literature were also evaluated. Ox brain thromboplastins yielded normal values, whereas human tissue or recombinant human thromboplastins yielded only slightly higher levels of activity than those obtained with rabbit brain reagents. The ox brain versus rabbit brain ratio was about 22, whereas the ratio for human placenta or human recombinant versus rabbit brain thromboplastin was only about 5. The FVII antigen versus rabbit brain, human tissue and ox brain activity ratios were 24.8, 4.3 and 1.1, respectively. These results indicate that the ox brain versus the rabbit brain thromboplastin ratio supplies a wider difference than the one between human tissue and rabbit brain. The antigen/ox brain activity ratio of 1.1 fully confirms this assertion.

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“…Bernardi et al [17] have previously reported a missense mutation (Cys310Phe) in two unrelated pedigrees. A disulfide bond formed by Cys310 and Cys329 is highly conserved in serine protease, although the composition of the loop residues is variable.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Cys329Gly Mutation Causing Hereditary Factor VII Deficiency

Tu²,

Lian³

et al. 2006

Acta Haematol

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We have previously reported a homozygous Cys329Gly mutation in a Chinese patient with factor VII (FVII) deficiency. Others have found a heterozygous Cys329Gly mutation in the F7 gene from patients of three different pedigrees. However, none of the reports included the expression and characterization of the mutant FVII in vitro. To investigate the effect of Cys329Gly on FVII function, we carried out transient transfections of baby hamster kidney cells (BHK-21) with a mutant FVII construct and compared the results to those obtained using a wild-type FVII construct and vector control. The results demonstrate that the level of FVII:Ag secreted into the medium by transfected BHK-21 cells with mutant construct was not affected, but the coagulation activity of the mutant FVII was undetectable. We conclude that Cys329 is critical to FVII coagulation, and the replacement of cysteine 329 by glycine leads to the loss of coagulation activity in the patients, possibly the molecular basis for FVII deficiency in the patients.

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Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII

Cited by 57 publications

References 36 publications

A rare inherited coagulation disorder: Combined homozygous factor VII and factor X deficiency

A rare inherited coagulation disorder: Combined homozygous factor VII and factor X deficiency

Ox Brain versus Rabbit Brain Thromboplastin Assays Are the Best Tool for a Preliminary Diagnosis of the Arg304Gln Factor VII Defect (FVII Padua)

Characterization of a Cys329Gly Mutation Causing Hereditary Factor VII Deficiency

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