The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort

Rabelo, Fabíola; Jardim, Letícia Lemos; Landau, Meytal; Gadelha, Telma; Corrêa, M. F. B.; Pereira, Igor Figueiredo; Rezende, Suely Meireles

doi:10.1111/hae.12645

Cited by 9 publications

(17 citation statements)

References 27 publications

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“…tients with one spontaneous bleeding (Grade II according to Peyvandi) were classified as Mild in ▶ Table 2 B, although there was an overlapping distribution when scores were related to FVII:C levels (▶ Figure 1 A and B). The genotype-phenotype relationship in FVII deficiency has been analysed in several smaller cohorts (27)(28)(29)(30)(31)(32)(33)(34). The results of the present study confirm and extend, in a homogeneously studied and genotyped cohort, the clinical and molecular variability of the disease and the type of symptoms described by other authors.…”

Section: Quintavalle Et Al F7 Gene Variants In Fvii Deficiencysupporting

confidence: 87%

F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency

Quintavalle¹,

Riccardi²,

Rivolta³

et al. 2017

Thromb Haemost

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Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:C<50 %. One hundred twenty-three probands were genotyped for F7 mutations and three polymorphic variants and classified according to recently published clinical scores. Forty out of 123 patients (33 %) were symptomatic (43 bleedings). A severe bleeding tendency was observed only in patients with FVII:C<0.10 %. Epistaxis (11 %) and menorrhagia (32 % of females in fertile age) were the most frequent bleedings. Molecular analysis detected 48 mutations, 20 not reported in the F7 international databases. Most mutations (62 %) were missense, large deletions were 6.2 %. Compound heterozygotes/homozygotes for mutations presented lower FVII:C levels compared to the other classes (Chi=43.709, p<0,001). The polymorphisms distribution was significantly different among the three F7 genotypic groups (Chi=72.289, p<0,001). The presence of truncating mutations was associated with lowest FVII:C levels (Chi=21.351, p=0.002). This study confirms the clinical and molecular variability of the disease and the type of symptoms. It shows a good correlation between the type of F7 mutation and/or polymorphisms and FVII:C levels, without a direct link between FVII:C and bleeding tendency. The results suggest that large deletions are underestimated and that they represent a common mechanism of F7 gene inactivation which should always be investigated in the diagnostic testing for FVII deficiency.

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Section: Quintavalle Et Al F7 Gene Variants In Fvii Deficiencysupporting

confidence: 87%

F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency

Quintavalle¹,

Riccardi²,

Rivolta³

et al. 2017

Thromb Haemost

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“…As far as South American is concerned, at least 6 proven homozygotes have been reported (3 in Brazil and 3 in Argentina) [10][11][12]. The ethnic background was Caucasian in the cases studied in Argentina [11,12] but was not reported for the cases seen in Brazil [10].…”

Section: Resultsmentioning

confidence: 99%

“…On the contrary, all those seen in Brazil are probably of mixed origin, Caucasian in Southern Brazil (State of Santa Caterina, San Paolo and Rio Grande do Sul) and African-Brazilian in the States of Central and Northern Brazil [10,13].…”

Section: Methodsmentioning

confidence: 96%

“…Even southern Brazil regions (Rio Grande do Sul, Santa Caterina, Sao Paulo), received less African "forced" immigrants [10]. In this regard, it may be underlined that in a small study of 401 Southern African-Brazilians no Arg304Gln mutation was found [13].…”

Section: Methodsmentioning

confidence: 98%

“…Unfortunately, no ethnic indication is reported in the papers from Brazil [10,13] and therefore no sure conclusion can be drawn.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Factor VII Arg304Gln (FVII Padua) in North and South Americas: The Influence of Past "Forced" or Spontaneous Migrations

Girolami¹,

Ferrari²,

Cosi³

et al. 2019

Clin Hematol Res

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A FVII variant characterized by discrepant levels of FVII activity according to the thromboplastin used in the assay system was first described in Padua in 1978 [1]. Since that time the defect has been found in several parts of the world, mainly among the population of the Mediterranean countries and among the African-American population [2-5].The main features of the defect are: very low activity levels when rabbit brain thromboplastins are used in the assay system and near normal or slightly reduced levels when thromboplastins of human origin (placenta) or human recombinant reagents are used. When ox-brain thromboplastin is used the FVII level is perfectly normal [1]. FVII antigen is also normal. The mutation responsible for the defect, an Arg304Gln substitution, was found in 1991 [6,7]. Because of the past migratory patterns existing between the Mediterranean countries and the Americas it was thought useful to investigate the effect these patterns had on the diffusion of a FVII special defect. It is likely that "forced" or spontaneous emigration patterns have influenced the presence of the mutation in North and South America.

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Rare bleeding disorders: Real-world data from a Spanish tertiary hospital

Martínez-Carballeira,

Caro,

Bernardo

et al. 2024

Blood Cells, Molecules, and Diseases

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The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort

Cited by 9 publications

References 27 publications

F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency

F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency

Factor VII Arg304Gln (FVII Padua) in North and South Americas: The Influence of Past "Forced" or Spontaneous Migrations

Rare bleeding disorders: Real-world data from a Spanish tertiary hospital

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