First report of molecular diagnosis of Tunisian hemophiliacs A: Identification of 8 novel causative mutations
<p>Abstract</p> <p>Introduction</p> <p>Hemophilia A is an X linked recessive hemorrhagic disorder caused by mutations in the <it>F8</it> gene that lead to qualitative and/or quantitative deficiencies of coagulation factor VIII (FVIII). Molecular diagnosis of...
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| Main Authors: | , , , , , , , , , |
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| Format: | Book |
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BMC,
2012-08-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>Introduction</p> <p>Hemophilia A is an X linked recessive hemorrhagic disorder caused by mutations in the <it>F8</it> gene that lead to qualitative and/or quantitative deficiencies of coagulation factor VIII (FVIII). Molecular diagnosis of hemophilia A is challenging because of the high number of different causative mutations that are distributed throughout the large <it>F8</it> gene. Molecular studies of these mutations are essential in order to reinforce our understanding of their pathogenic effect responsible for the disorder.</p> <p>Aim</p> <p>In this study we have performed molecular analysis of 28 Tunisian hemophilia A patients and analyzed the <it>F8</it> mutation spectrum.</p> <p>Methods</p> <p>We screened the presence of intron 22 and intron 1 inversion in severe hemophilia A patients by southern blotting and polymerase chain reaction (PCR). Detection of point mutations was performed by dHPLC/sequencing of the coding <it>F8</it> gene region. We predict the potential functional consequences of novel missense mutations with bioinformatics approaches and mapping of their spatial positions on the available FVIII 3D structure.</p> <p>Results</p> <p>We identified 23 different mutations in 28 Tunisian hemophilia A patients belonging to 22 unrelated families. The identified mutations included 5 intron 22 inversions, 7 insertions, 4 deletions and 7 substitutions. In total 18 point mutations were identified, of which 9 are located in exon 14, the most mutated exonic sequence in the <it>F8</it> gene. Among the 23 mutations, 8 are novel and not deposited in the HAMSTeRS database nor described in recently published articles.</p> <p>Conclusion</p> <p>The mutation spectrum of Tunisian hemophilia A patients is heterogeneous with the presence of some characteristic features.</p> <p>Virtual slides</p> <p>The virtual slide(s) for this article can be found here:</p> <p><url>http://www.diagnosticpathology.diagnomx.eu/vs/1693269827490715</url></p> |
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| Item Description: | 10.1186/1746-1596-7-93 1746-1596 |