Novel characterization of a breakpoint in F8
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 mol...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , |
| التنسيق: | article |
| منشور في: |
2015
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/6656 http://dx.doi.org/10.1111/hae.12606 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://onlinelibrary.wiley.com/doi/10.1111/hae.12606/full |
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| _version_ | 1864513480598487040 |
|---|---|
| author | El-Maarri, O. |
| author2 | Williams, M.D. Pezeshkpoor, B. Theophilus, B.D.M. Guillatt, A.M. Oldenburg, J. |
| author2_role | author author author author author |
| author_facet | El-Maarri, O. Williams, M.D. Pezeshkpoor, B. Theophilus, B.D.M. Guillatt, A.M. Oldenburg, J. |
| author_role | author |
| dc.creator.none.fl_str_mv | El-Maarri, O. Williams, M.D. Pezeshkpoor, B. Theophilus, B.D.M. Guillatt, A.M. Oldenburg, J. |
| dc.date.none.fl_str_mv | 2015 2017-11-23T10:48:44Z 2017-11-23T10:48:44Z 2017-11-23 |
| dc.identifier.none.fl_str_mv | 1365-2516 http://hdl.handle.net/10725/6656 http://dx.doi.org/10.1111/hae.12606 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. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://onlinelibrary.wiley.com/doi/10.1111/hae.12606/full |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Haemophilia |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Novel characterization of a breakpoint in F8 an individualized approach to gene analysis when PCR and MLPA results contradic |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_98b45a36737cdb509a86250e81e655cc |
| identifier_str_mv | 1365-2516 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. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/6656 |
| publishDate | 2015 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Novel characterization of a breakpoint in F8an individualized approach to gene analysis when PCR and MLPA results contradicEl-Maarri, O.Williams, M.D.Pezeshkpoor, B.Theophilus, B.D.M.Guillatt, A.M.Oldenburg, J.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.PublishedN/A2017-11-23T10:48:44Z2017-11-23T10:48:44Z20152017-11-23Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1365-2516http://hdl.handle.net/10725/6656http://dx.doi.org/10.1111/hae.12606Pezeshkpoor, 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.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://onlinelibrary.wiley.com/doi/10.1111/hae.12606/fullenHaemophiliainfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/66562021-03-19T10:03:28Z |
| spellingShingle | Novel characterization of a breakpoint in F8 El-Maarri, O. |
| status_str | publishedVersion |
| title | Novel characterization of a breakpoint in F8 |
| title_full | Novel characterization of a breakpoint in F8 |
| title_fullStr | Novel characterization of a breakpoint in F8 |
| title_full_unstemmed | Novel characterization of a breakpoint in F8 |
| title_short | Novel characterization of a breakpoint in F8 |
| title_sort | Novel characterization of a breakpoint in F8 |
| url | http://hdl.handle.net/10725/6656 http://dx.doi.org/10.1111/hae.12606 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://onlinelibrary.wiley.com/doi/10.1111/hae.12606/full |