First report of molecular diagnosis of Tunisian hemophiliacs A: identification of 8 novel causative mutations

IntroductionHemophilia A is an X linked recessive hemorrhagic disorder caused by mutations in the F8gene 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 ofdifferent causative mutations that are distributed throughout the large F8 gene.

Molecularstudies of these mutations are essential in order to reinforce our understanding of theirpathogenic effect responsible for the disorder.AimIn this study we have performed molecular analysis of 28 Tunisian hemophilia A patients andanalyzed the F8 mutation spectrum.

Methods: We screened the presence of intron 22 and intron 1 inversion in severe hemophilia A patientsby southern blotting and polymerase chain reaction (PCR). Detection of point mutations wasperformed by dHPLC/sequencing of the coding F8 gene region.

We predict the potentialfunctional consequences of novel missense mutations with bioinformatics approaches andmapping of their spatial positions on the available FVIII 3D structure.

Results: We identified 23 different mutations in 28 Tunisian hemophilia A patients belonging to 22unrelated families. The identified mutations included 5 intron 22 inversions, 7 insertions, 4deletions and 7 substitutions.

In total 18 point mutations were identified, of which 9 arelocated in exon 14, the most mutated exonic sequence in the F8 gene. Among the 23mutations, 8 are novel and not deposited in the HAMSTeRS database nor described inrecently published articles.

Conclusion: The mutation spectrum of Tunisian hemophilia A patients is heterogeneous with the presenceof some characteristic features.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1693269827490715

Author: Hejer ElmahmoudiHoussein Khodjet-el-khilEdvard WigrenAsma JliziKaouther ZahraDorothé PellechiaChristine VinciguerraBalkis MeddebAmel Elgaaied Ben AmmarEmna Gouider
Credits/Source: Diagnostic Pathology 2012, 7:93

Published on: 2012-08-10

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