Mutation Analysis in <i>F9</i> Gene of 17 Families with Haemophilia B from Iran

Enayat, M. S.; Karimi, Mehran; Chana, Gabis; Farjadian, Shirin; Theophilus, Bimal D. M.; Hill, F. G. H.

doi:10.1111/j.1365-2516.2004.01041.x

Cited by 7 publications

(3 citation statements)

References 16 publications

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“…The advent of molecular genetics has had a significant impact on carrier detection and prenatal diagnosis in haemophilia and other bleeding disorders. Though the direct mutation detection technique has been employed in most of the laboratories for offering an accurate diagnosis in the western countries [1,2], DNA polymorphism analysis has become the mainstay of diagnosis in developing countries like India [3–5].…”

Section: Introductionmentioning

confidence: 99%

Robustness of factor assays following cordocentesis in the prenatal diagnosis of haemophilia and other bleeding disorders

Shetty

Ghosh

2007

Haemophilia

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Prenatal diagnosis is the generally accepted option for genetic disorders including haemophilias and other bleeding disorders. Cord blood analysis between 17.4 and 20.6 weeks of gestation was performed in 172 confirmed carriers belonging to families of haemophilia A, haemophilia B, von Willebrand disease (VWD), factor VII and X deficiency; 133 were carriers for haemophilia A, 30 for haemophilia B, six for type 3 VWD, two for FX deficiency and one for FVII deficiency. The approach to the cord was either transabdominal or transamniotic. The volume of blood collected varied between 1 and 2 mL. In case of haemophilias, the diagnosis was offered by factor VIII/IX:C activity and antigen assays wherever required. In case of VWD, the diagnosis was based on von Willebrand factor antigen assays as detected by ELISA along with FVIII:C assay while in cases of FVII and FX deficiency, the diagnosis was based on FVII:C and FX:C respectively. The factor levels were compared with the normal range established in the laboratory for different coagulation factors between 18 and 21 weeks of gestation in women tested for other haematological disorders. Only in two cases, the procedure had to be repeated for reasons of extensive maternal contamination. All the deliveries have been followed up and the diagnoses reconfirmed by repeat clotting factor assays and DNA analysis whenever informative. Simple precautions like collection of fetal blood samples in smaller volumes in separate tubes, assaying multiple coagulation factors in the fetal blood samples helped us to offer diagnoses in all the women analysed. No fetal death or abortion was reported following the procedure. We suggest that accurate fetal blood sampling is a safe technique for the diagnosis of many of the bleeding disorders in places where genetic diagnostic services are not available.

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Section: Introductionmentioning

confidence: 99%

Robustness of factor assays following cordocentesis in the prenatal diagnosis of haemophilia and other bleeding disorders

Shetty

Ghosh

2007

Haemophilia

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“…More than 1,000 mutations have been reported for factor IX to date (Factorix.org; http://hadb.org.uk). Literature review shows that there are no studies reporting for factor IX mutations in Saudi population, or in the Middle Eastern population except from Iran, by Karimipoor et al, and Enayat et al [ 47 , 48 ]. Our study is the first study of molecular genetic analysis of the factor IX gene in Saudi Arabian patients.…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies

et al. 2017

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BackgroundHemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation.MethodsFor genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; http://www.charmm-gui.org) and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation.ResultsSix mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs.ConclusionThe protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia.

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“…PCR is used for common variants (32) and sequencing for rare variants. The F9 gene sequencing can be performed through Sanger sequencing (33) or next generation sequencing (NGS) technologies (34).…”

Section: Figurementioning

confidence: 99%

Current therapeutic approaches in the management of hemophilia—a consensus view by the Romanian Society of Hematology

et al. 2021

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Hemophilia A (HA) and hemophilia B (HB) are rare disorders, being caused by the total lack or under-expression of two factors from the coagulation cascade coded by genes of the X chromosome. Thus, in hemophilic patients, the blood does not clot properly. This results in spontaneous bleeding episodes after an injury or surgical intervention. A patient-centered regimen is considered optimal. Age, pharmacokinetics, bleeding phenotype, joint status, adherence, physical activity, personal goals are all factors that should be considered when individualizing therapy. In the past 10 years, many innovations in the diagnostic and treatment options were presented as being either approved or in development, thus helping clinicians to improve the standard-of-care for patients with hemophilia. Recombinant factors still remain the standard of care in hemophilia, however they pose a challenge to treatment adherence because they have short halflife, which where the extended half-life (EHL) factors come with the solution, increasing the half-life to 96 hours. Gene therapies have a promising future with proven beneficial effects in clinical trials. We present and critically analyze in the current manuscript the pros and cons of all the major discoveries in the diagnosis and treatment of HA and HB, as well as identify key areas of hemophilia research where improvements are needed.

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Mutation Analysis in F9 Gene of 17 Families with Haemophilia B from Iran

Cited by 7 publications

References 16 publications

Robustness of factor assays following cordocentesis in the prenatal diagnosis of haemophilia and other bleeding disorders

Robustness of factor assays following cordocentesis in the prenatal diagnosis of haemophilia and other bleeding disorders

Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies

Current therapeutic approaches in the management of hemophilia—a consensus view by the Romanian Society of Hematology

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