Spectrum of factor VIII mutations in Arab patients with severe haemophilia A

Abu-Amero, Khaled K.; Hellani, Ali; Al-Mahed, M.; Al-Sheikh, Iman H.

doi:10.1111/j.1365-2516.2008.01690.x

Cited by 14 publications

(18 citation statements)

References 7 publications

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“…This mutation c.409 A>C, p.(T137P); (ACC>CCC) is associated with severe form of haemophillia (33,34). Both cases have factor VIII base line levels of <1%, and have chronic joint disabilities patient also had HIV and was a diabetic.…”

Section: Analysis Of Samples For Inversion 22 In Factor VIII Genementioning

confidence: 99%

“…Several studies are available in literature describing the mutations in factor VIII gene, from many ethnic groups and different populations [16,17,25,29,30]. Recently, some reports were published from Middle Eastern countries also describing factor VIII gene mutations [31][32][33][34]. However, the spectrum and nature of common mutations causing hemophilia A in Arab population specifically in Saudi Arabs is not clear.…”

Section: Page 2 Of 11mentioning

confidence: 99%

“…There is no extensive study to describe the prevalence of inv-22 in Saudi patients. One report by Abu-Amero, et al (34) used only six cases from Saudi Arabia in a total of 20 Arab patients for analysis on inv-22, and reported 45% are positive.…”

Section: Page 9 Of 11mentioning

confidence: 99%

See 2 more Smart Citations

Mutation Screening of the Factor VIII Gene in Hemophilia A in Saudi Arabia: Two Novel Mutations and Genotype-Phenotype Correlation

Al‐Allaf¹,

Taher²,

Abduljaleel³

et al. 2016

J Mol Genet Med

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Section: Analysis Of Samples For Inversion 22 In Factor VIII Genementioning

confidence: 99%

Section: Page 2 Of 11mentioning

confidence: 99%

See 1 more Smart Citation

Mutation Screening of the Factor VIII Gene in Hemophilia A in Saudi Arabia: Two Novel Mutations and Genotype-Phenotype Correlation

Al‐Allaf¹,

Taher²,

Abduljaleel³

et al. 2016

J Mol Genet Med

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“…The PCR amplifications were carried out using previously described primers by Abu-Amero et al [2], 2008 and Pavlova et al [11], 2008. The primers were specifically designed to amplify promoter, coding exons and flanking intronic regions F8.…”

Section: F8 Mutation Analysismentioning

confidence: 99%

“…The gene consists of 26 exons, transcribed into a 9 kb mRNA and encodes 2351 amino acids. The molecular pathology of the gene plays a determinant role in the development of the disease, different types of mutations had been reported in patients with hemophilia A [2][3][4][5][6]. Although about half of all severe factor VIII deficiencies are caused by gene rearrangements (inversions) involving intron 22 [7,8], other mutations like point mutation, large deletions and insertions have been reported in a comprehensive mutation database (URL:http://europium.csc.mrc.ac.uk/; last updated August 2007).…”

Section: Introductionmentioning

confidence: 99%

Molecular genotyping of hemophilia A in Saudi Arabia: report of 2 novel mutations

Owaidah¹,

Alkhail²,

Zahrani

et al. 2009

Blood Coagulation &Amp; Fibrinolysis

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Different types of mutations have been reported in patients with hemophilia A. Although about half of all severe factor VIII deficiencies are caused by gene rearrangements (inversions) involving intron 22 in F8, other mutations such as point mutation, large deletions and insertions had been reported. We report the result of the first molecular testing for or F8 mutations from Saudi Arabia. A cohort of 22 men with hemophilia A was studied for F8 mutations. All patients were tested for factor VIII coagulant activity and inhibitors. Peripheral blood samples were used for DNA extraction followed by PCR detection of intron 22 inversion and all samples tested negative were screened for other F8 mutations. The patient's age ranged between 4 and 37 years. All patients except two siblings had severe hemophilia A. Only two patients out of 22 developed inhibitors with no obvious relation to the genotype. F8 Intron 22 inversion was detected in 10 patients (50%) of severe cases. Additionally, five point mutations and one deletion/insertion involving different exons were detected. All identified mutations were associated with severe phenotype except for one, which was associated with mild phenotype of hemophilia. This is the first report of molecular genotype of hemophilia A in the Saudi population and one of the few for Arab population. We had confirmed the incidence of Inversion 22 in severe hemophilia. We are reporting two novel mutations in F8, which can be used for carrier detection and prenatal genetic diagnosis (PGD).

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Genotyping of intron 22-related rearrangements of F8 by inverse-shifting PCR in Egyptian hemophilia A patients

Abou-Elew

Ahmed²,

Raslan

et al. 2010

Ann Hematol

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Hemophilia A (HA) is the most common severe bleeding disorder in humans, affecting one in 5,000 male births. In severe HA, intron 22 inversion of F8 is the most prevalent mutation, accounting for 40-50% of all mutations; however, little is known about the disease-causing mutations among Egyptian hemophiliacs. We aimed at genotyping all possible known DNA rearrangements of intron 22 of F8 in Egyptian HA patients. Peripheral blood samples were collected from 30 Egyptian HA patients (13 severe, ten moderate, and seven mild cases). Genotyping of F8 intron 22 rearrangements was performed by inverse-shifting PCR (IS-PCR). Our study revealed that seven patients (23.3%) had inversion 22, three patients (10%) had deletion 22, and 20 patients (66.7%) carried the wild-type allele. No intron 22 duplication was detected. The relative proportion of inversion 22-type 1 to inversion 22-type 2 was 85.7% and 14.3%, respectively, whereas the relative proportion of deletion 22-type 1 to deletion 22-type 2 was 33.3% and 66.7%, respectively. A statistically highly significant relation was found between disease severity and F8 intron 22 rearrangements (p = 0.008). Among severe cases, 46.1% had inversion 22, 23.1% had deletion 22, and 30.8% carried the wild-type allele. We conclude that F8 intron 22 inversion/deletion is responsible for about one third of disease-causing mutations among Egyptian hemophiliacs and for nearly 70% in severe cases. In addition, F8 intron 22 inversion/deletion by IS-PCR has proven to be a rapid and robust technique and might be the recommended tool for genetic analysis of HA patients specially with severe cases in developing countries.

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Spectrum of factor VIII mutations in Arab patients with severe haemophilia A

Cited by 14 publications

References 7 publications

Mutation Screening of the Factor VIII Gene in Hemophilia A in Saudi Arabia: Two Novel Mutations and Genotype-Phenotype Correlation

Mutation Screening of the Factor VIII Gene in Hemophilia A in Saudi Arabia: Two Novel Mutations and Genotype-Phenotype Correlation

Molecular genotyping of hemophilia A in Saudi Arabia: report of 2 novel mutations

Genotyping of intron 22-related rearrangements of F8 by inverse-shifting PCR in Egyptian hemophilia A patients

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