scholarly journals Identification of the Intron 22 and Intron 1 Inversions of the Factor VIII Gene in Iraqi Kurdish Patients With Hemophilia A

2020 ◽  
Vol 26 ◽  
pp. 107602961988829 ◽  
Author(s):  
Aveen M. Raouf Abdulqader ◽  
Ali Ibrahim Mohammed ◽  
Shwan Rachid ◽  
Peyman Ghoraishizadeh ◽  
Sarwar Noori Mahmood
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Causative Mutation ◽  
Coagulation Disorder ◽  
Phenotype Correlation ◽  
Factor Viii Gene ◽  
Intron 1 ◽  
Pcr Method ◽  
Polymerase Chain ◽  
And Inversion

Hemophilia A (HA) is a severe coagulation disorder affecting 1 in 5000 to 10 000 male births. In severe cases, the most deleterious large DNA rearrangements are inversions of intron 22 (Inv22) and intron 1 (Inv1) of the factor VIII (FVIII) gene. These account for 40% to 50% and 1% to 5% of all causative mutations, respectively. Nevertheless, no genetic analysis to identify the actual causative mutation of FVIII, particularly Inv22 and Inv1, among Iraqi Kurdish hemophiliacs has been performed. In this study, we aimed to genotype Inv22 and Inv1 of the FVIII gene in our patients with HA and reveal the genotype/phenotype correlation with the inversion mutations and their role as a risk factor for the development of inhibitors. Analyses of the Inv22 and Inv1 mutations in 80 Iraqi Kurdish patients with HA (60 severe, 18 moderate, and 2 mild) were performed using the inverse shifting–polymerase chain reaction (IS-PCR) method. In severe cases, 46.7% (28/60) had Inv22 and 3.3% (2/60) had Inv1. The genotype/phenotype relation of Inv22 and Inv1 illustrated a statistically significant association ( P = .012) between disease severity and inversion mutations. Slightly more patients with Inv22 (39%) developed inhibitors than those without Inv22 (28%; odds ratio = 1.65, 95% confidence interval = 0.56-4.87, P = .361). Inv22 is a major cause of severe HA in Iraqi Kurdish patients, and IS-PCR is a rapid, robust, and effective method that can be applied for carrier detection and prenatal diagnosis of HA in developing countries.

Molecular analysis of FVIII gene in severe HA patients of Costa Rica

2010 ◽  
Vol 30 (S 01) ◽  
pp. S150-S152
Author(s):  
G. Jiménez-Cruz ◽  
M. Mendez ◽  
P. Chaverri ◽  
P. Alvarado ◽  
W. Schröder ◽  
...  
Keyword(s):  
Factor Viii ◽  
Coagulation Factor ◽  
Costa Rican ◽  
Factor Viii Gene ◽  
Intron 22 Inversion ◽  
Intron 1 ◽  
Polymerase Chain ◽  
Inversion Analysis

SummaryHaemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII (FVIII). It is caused by FVIII gene intron 22 inversion (Inv22) in approximately 45% and by intron 1 inversion (Inv1) in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous regions, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The aim of this study was to analyze the presence of these mutations in 25 HA Costa Rican families. Patients, methods: We studied 34 HA patients and 110 unrelated obligate members and possible carriers for the presence of Inv22or Inv1. Standard analyses of the factor VIII gene were used incl. Southern blot and long-range polymerase chain reaction for inversion analysis. Results: We found altered Inv22 restriction profiles in 21 patients and 37 carriers. It was found type 1 and type 2 of the inversion of Inv22. During the screening for Inv1 among the HA patient, who were Inv22 negative, we did not found this mutation. Discussion: Our data highlight the importance of the analysis of Inv22 for their association with development of inhibitors in the HA patients and we are continuous searching of Inv1 mutation. This knowledge represents a step for genetic counseling and prevention of the inhibitor development.

Intron 1 factor VIII gene inversion in a population of Italian hemophilia A patients

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3432-3432 ◽  
Author(s):  
Federica Riccardi ◽  
Annarita Tagliaferri ◽  
Cesare Manotti ◽  
Corrado Pattacini ◽  
Tauro Maria Neri
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Viii Gene ◽  
Intron 1

scholarly journals Detection of Intron22 Mutations in Iraqi Female Carriers in Wasit City with Hemophilia A

2017 ◽  
pp. 13-24
Author(s):  
Maysoon Mohammed Hassan
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Gene Identification ◽  
Severe Hemophilia ◽  
Factor Viii Gene ◽  
Intron 1 ◽  
Detection Mechanisms ◽  
Female Carriers ◽  
Chromosomal Recombination

The background:One of the prevalent main concerns in the medical world is the identification of Intron22 mutations in the Factor VIII gene carried by Iraqi patient in Wasit town, in Iraq suffering Hemophilia A (classical hemophilia) which is related to a X-chromosome recessive haemorrhage afflictions as the result of a flaw in the coagulation factor VIII (FVIII). It is essentially related with F8 mutations of Intron22 in version which forms the most typical kind of mutations of blood afflictions worldwide involving half the patients suffering from severe Hemophilia A that possesses mutations, in addition to Intron 1 inversion suffered by 5% of severe Hemophilia A patients.All of the inversion mutations are suffered mainly by males,and uncommonly by females due to the intra chromosomal recombination among the homologous areas, in inversion 1 or 22, with extragenic copy posited the telomeric to the Factor VIII gene. Unfortunately, there is an absence in Iraq on researches pertaining blood affliction gene identification in persons who carries the Intron22 mutations exception in the current research.Aims of study:The objectives of the research is to to analyze through the detection mechanisms, the existence of Intron 22 mutations in the Factor VIII gene of 10 Hemophilia A Iraqi carriers cohort families. The hypothesis and anticipated result is that there will be a minimal margin of hazardous possibility for the recurrence. The hereditary F8 mutation is unknown to be present on the maternal side of the patient sufferer due to the possibilty of germline mosaics that exists within the community.

Methylation analysis of the promoter region and intron 1 of the factor VIII gene in haemophilia A patients

2013 ◽  
Vol 33 (S 01) ◽  
pp. S46-S49
Author(s):  
T. Hansmann ◽  
T. Haaf ◽  
J. Oldenburg ◽  
C. R. Müller ◽  
S. Rost ◽  
...  
Keyword(s):  
Factor Viii ◽  
Coagulation Disorder ◽  
Haemophilia A ◽  
Methylation Analysis ◽  
Factor Viii Gene ◽  
Mutation Status ◽  
Bisulfite Pyrosequencing ◽  
Intron 1 ◽  
Methylation Patterns ◽  
Promoter Mutations

SummaryHaemophilia A is the most common X-linked inherited coagulation disorder caused by a deficiency of the factor VIII protein (FVIII). A plethora of different mutations in the factor VIII gene (F8) have been identified as causative for this bleeding disease including a few promoter mutations. However, in approximately 2–5% of all haemophilic patients, the causal mutation still remains unknown. To our knowledge, epigenetic abnormalities in regulatory regions of the F8 gene have not yet been implicated in the disease pathogenesis.We therefore developed bisulfite pyrosequencing assays to screen patients with unknown mutation status for their methylation patterns in presumed regulative regions of the F8 gene (5’UTR and intron 1). The methylation patterns of haemophilia A patients did not differ from that of controls. In three patients, chromosomal aberrations were identified which could be associated with a defective FVIII synthesis.

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