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Analysis of mRNA in hemophilia A patients with undetectable mutations reveals normal splicing in the factor VIII gene

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dc.contributor.author El-Maarri, O.
dc.contributor.author Herbiniaux, U.
dc.contributor.author Graw, J.
dc.contributor.author Schroder, J.
dc.contributor.author Terzic, A.
dc.contributor.author Watzka, M.
dc.contributor.author Brackmann, H.H.
dc.contributor.author Schramm, W.
dc.contributor.author Hanfland, P.
dc.contributor.author Schwaab, R.
dc.contributor.author Muller, C.R.
dc.contributor.author Oldenburg, J.
dc.date.accessioned 2017-11-23T11:08:28Z
dc.date.available 2017-11-23T11:08:28Z
dc.date.copyright 2005 en_US
dc.identifier.issn 1538-7836 en_US
dc.identifier.uri http://hdl.handle.net/10725/6657
dc.description.abstract Background: haemophilia A (HA) is characterized by partial or total deficiency of factor VIII (FVIII) protein activity. It is caused by a broad spectrum of mutations in the FVIII gene. Despite tremendous improvements in mutation screening methods, in about 2% of HA patients no DNA change could be found, even after sequencing the whole coding part of the FVIII gene including the flanking splice sites, as well as the promotor and the 3′ UTR regions. Objectives, patients and methods: In the present study we performed a detailed RNA analysis of three groups of patients. The first included control patients with known splicing defects, the second included two patients with already identified nucleotide changes close to splicing sites, that could potentially alter the normal splicing process, and a third group of 11 unrelated patients whose genomic DNA have already been screened for mutations by DHPLC and direct sequencing with no mutation being identified. Results: Both candidate splice site mutations were shown to result in either skipping or alternative splicing of at least one exon, therefore these DNA changes must be considered as causal for the patients' HA phenotype. In contrast, no abnormalities on the RNA level were observed in any of 11 unrelated patients without mutations in the FVIII gene. Conclusions: These findings exclude mutations that could be located deep in the introns and affecting either normal splicing or lead to mechanisms causing some unknown rearrangements of the FVIII gene. In fact, our results point to the presence of still unknown factor(s) causing HA, which might be either allelic or in the close proximity of the FVIII gene or non-allelic associated with other genetic loci that are involved in the processing of the FVIII protein. en_US
dc.language.iso en en_US
dc.title Analysis of mRNA in hemophilia A patients with undetectable mutations reveals normal splicing in the factor VIII gene en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201508713 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Journal of Thrombosis and Haemostasis en_US
dc.journal.volume 3 en_US
dc.journal.issue 2 en_US
dc.article.pages 332-339 en_US
dc.keywords Factor VIII en_US
dc.keywords Haemophilia A en_US
dc.keywords RNA analysis en_US
dc.keywords Splicing mutations en_US
dc.identifier.doi http://dx.doi.org/10.1111/j.1538-7836.2005.01140.x en_US
dc.identifier.ctation El-Maarri, O., Herbiniaux, U., Graw, J., Schröder, J., Watzka, M., Brackmann, H. H., ... & Oldenburg, O. (2005). Analysis of mRNA in hemophilia A patients with undetectable mutations reveals normal splicing in the factor VIII gene. J Thromb Haemost, 3, 332-339. en_US
dc.author.email osman.elmaarri@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://ku7rj9xt8c.scholar.serialssolutions.com/?sid=google&auinit=O&aulast=El-Maarri&atitle=Detailed+RNA+analysis+in+haemophilia+A+patients+with+previously+undetectable+mutations&title=Journal+of+thrombosis+and+haemostasis&volume=3&date=2005&spage=332&issn=1538-7933 en_US
dc.author.affiliation Lebanese American University en_US


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