Novel characterization of a breakpoint in F8

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dc.contributor.author El-Maarri, O.
dc.contributor.author Williams, M.D.
dc.contributor.author Pezeshkpoor, B.
dc.contributor.author Theophilus, B.D.M.
dc.contributor.author Guillatt, A.M.
dc.contributor.author Oldenburg, J.
dc.date.accessioned 2017-11-23T10:48:44Z
dc.date.available 2017-11-23T10:48:44Z
dc.date.copyright 2015 en_US
dc.date.issued 2017-11-23
dc.identifier.issn 1365-2516 en_US
dc.identifier.uri http://hdl.handle.net/10725/6656
dc.description.abstract Haemophilia A is an X-linked bleeding disorder caused by heterogeneous mutations in the F8 gene. Two inversion hotspots in intron 22 and intron 1, as well as point mutations, small insertions and deletions in the F8 gene account for causal mutations leading to severe haemophilia A. Rarely, novel molecular mechanisms lead to a haemophilia A phenotype which cannot be completely characterized by routine molecular diagnostic methods. Here, we characterized the molecular abnormality in a boy with a severe haemophilia A phenotype. On investigation by PCR and DNA sequencing, exon 18 of F8 repeatedly failed to amplify. However, analysis by multiplex ligation-dependent probe amplification demonstrated the presence of exon 18 sequence, suggesting a more complex rearrangement than a single exon deletion. The analysis of exon 18 and its flanking regions by inverse PCR revealed a complex mutation comprising insertions of extragenic sequences from Xq28 along with a partial duplication of exon 18. Based on the successful analysis and characterization of the familial breakpoint, we developed a PCR-based diagnostic approach to detect this defect in family members in whom no diagnostic test could be offered until this time. en_US
dc.language.iso en en_US
dc.title Novel characterization of a breakpoint in F8 en_US
dc.type Article en_US
dc.description.version Published en_US
dc.title.subtitle an individualized approach to gene analysis when PCR and MLPA results contradic 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 Haemophilia en_US
dc.journal.volume 21 en_US
dc.journal.issue 3 en_US
dc.article.pages 329-397 en_US
dc.keywords Breakpoint en_US
dc.keywords Gene rearrangement en_US
dc.keywords HaemophiliaA en_US
dc.keywords Inverse PCR en_US
dc.keywords Multiplex ligation-dependent probe amplification en_US
dc.identifier.doi http://dx.doi.org/10.1111/hae.12606 en_US
dc.identifier.ctation Pezeshkpoor, B., Theophilus, B. D. M., Guilliatt, A. M., Oldenburg, J., Williams, M. D., & El‐Maarri, O. (2015). Novel characterization of a breakpoint in F8: an individualized approach to gene analysis when PCR and MLPA results contradict. Haemophilia, 21(3), 392-397. 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://onlinelibrary.wiley.com/doi/10.1111/hae.12606/full en_US
dc.author.affiliation Lebanese American University en_US

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