Identification of genetic defects underlying FVII deficiency in 10 patients belonging to eight unrelated families of the North provinces from Tunisia

Elmahmoudi, Hejer; Ben-lakhal, Fatma; Elborji, Wijden; Jlizi, Asma; Zahra, Kaouther; Sassi, R.; Zorgan, Moez; Meddeb, Balkis; Ammar, Amel Elgaaied Ben; Gouider, Emna

doi:10.1186/1746-1596-7-92

Cited by 7 publications

(10 citation statements)

References 20 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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“…According to the annual global survey 2014, Tunisia reported 80 cases with GT and our center followed 35 of them (43.75%). In other studies concerning autosomal bleeding disorders (FVII deficiency, FV + FVIII deficiency and FXIII deficiency), we also reported higher incidence in our country resulting from the consanguineous marriage [10][11][12]. These data give us specificity for bleeding disorders.…”

Section: Discussionsupporting

confidence: 56%

The Glanzmann’s Thrombasthenia in Tunisia: A Cohort Study

et al. 2017

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Background: The Glanzmann's thrombasthenia (GT) is a rare autosomal-recessive bleeding disorder with uncommon neonatal revelation. It is due to abnormalities of quantitative and/or qualitative α IIb β 3 integrin. This cell adhesion receptor is essential for platelet aggregation and allows the formation of a hemostatic plug if the vessel is damaged by injury. The clinical picture of GT is variable, with mucocutaneous bleeding due to non-functional platelets. Management requires a good expertise in bleeding disorders. We describe the clinical and the epidemiological data of GT in Aziza Othmana Hospital Hemophilia Center.

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“…Cons: Consanguinity/ ∗∗ Elmahmoudi H, Ben-Lakhal F, Elborji W, et al [17]/ ND, not determined/Pathogeneous mutations are represented in bold/ ∗ Novel variant/ P0, no insertion of 10 bp at position-323 in the promoter; P1, insertion of 10 bp at position-323 in promoter/A1, nt C at position −122 in the promoter; A2, nt T at position −122 in promoter/G: nt G at position 73 in Intron1; A: nt A at position 73 in Intron1/H1, allele His 175 CAC; H2:allele His 175 CAT/G, nt G at position c.806; A, nt A at position c.806/M1, Arg at.…”

Section: Resultsmentioning

confidence: 99%

“…This study was conducted in patients with congenital FVII deficiency of haemophilia treatment centre of Aziza Othmana hospital. Data, including consanguinity, circumstances of diagnosis, age at the diagnosis and bleeding manifestations, were gathered from the regional registry of bleeding disorders and the medical file of each patient [17,18]. All patients provided their informed consent, and the study was approved by the hospital medical ethical committee.…”

Section: Patientsmentioning

confidence: 99%

Clinical phenotype and F7 gene genotype in 40 Tunisian patients with congenital factor VII deficiency

Ouardani

Elmahmoudi

ElBorgi

et al. 2022

Blood Coagulation &Amp; Fibrinolysis

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Congenital factor VII (FVII) deficiency is an autosomal recessive bleeding disorder characterized by a weak phenotypic and genotypic correlation. This study aimed to determine the genetic alterations of 40 Tunisian patients and to evaluate their relationships with the collected clinical and biological data. Forty FVII-deficient Tunisian patients have been included in this study. First, diagnosis of the FVII deficiency was made on the basis of FVII coagulant activity (FVII:c) levels performed using the prothrombin time assay. Then, clinical and anamnesis data were set up and filed out from the regional registry of bleeding disorders and the medical file of each patient. Finally, genetic alterations were determined by direct sequencing of the coding regions, intron/exons boundaries of the F7 gene. Clinical heterogeneity was noticed, and the direct sequencing allowed the identification of 13 F7 gene mutations of which one was a novel mutation. The clinical manifestations are variably associated with FVII activity FVII:c levels. Lack of relations between severity of clinical manifestations and genotypes was observed; however, a relationship between the nonpathogeneous mutations and clinical phenotypes was noticed. A wide phenotypic inter-individual variability was detected, which suggests the presence of other extragenetic components influencing the expressivity of the deficiency.

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Identification of genetic defects underlying FVII deficiency in 10 patients belonging to eight unrelated families of the North provinces from Tunisia

Cited by 7 publications

References 20 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

The Glanzmann’s Thrombasthenia in Tunisia: A Cohort Study

Clinical phenotype and F7 gene genotype in 40 Tunisian patients with congenital factor VII deficiency

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