Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients
Abstract Background Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (F8) deficiency. F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational pa...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-02-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1575 |
| _version_ | 1797301054617944064 |
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| author | Rehab M. Mosaad Khalda S. Amr Eman A. Rabie Naglaa O. Mostafa Sonia A. Habib Ghada Y. El‐Kamah |
| author_facet | Rehab M. Mosaad Khalda S. Amr Eman A. Rabie Naglaa O. Mostafa Sonia A. Habib Ghada Y. El‐Kamah |
| author_sort | Rehab M. Mosaad |
| collection | DOAJ |
| description | Abstract Background Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (F8) deficiency. F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational patterns. This study aims to identify F8 gene mutations among Egyptian HA patients. Methods DNA samples from 60 HA patients were screened for int22 and int1 rearrangements using simplified inverse shifting PCR (IS‐PCR) followed by exon 14 sequencing. Also, four uncharacterized patients were studied by targeted exome sequencing. Results In 33.3% of the studied patients, we identified three int22 rearrangements, three exon 14 mutations (two frameshift; one novel (NM_000132.3:c.2734_2735delAA, p.(N912Ffs*6)), a second reported mutation (NM_000132.3:c.3091_3094delAGAA, p.(K1031Lfs*9)), and one nonsense mutation (NM_000132.3:c.2440C>T, p.(R814*)). All identified mutations were detected in patients with severe HA phenotype. Targeted exome sequencing could not detect any known pathogenic variants. Conclusion Intron 22 rearrangement and exon 14 mutations correlate with most severe hemophilia A Egyptian patients. |
| first_indexed | 2024-03-07T23:15:54Z |
| format | Article |
| id | doaj.art-52f5c1ffa7df41dc9263349910215ee5 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:15:54Z |
| publishDate | 2021-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-52f5c1ffa7df41dc9263349910215ee52024-02-21T11:37:44ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-02-0192n/an/a10.1002/mgg3.1575Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patientsRehab M. Mosaad0Khalda S. Amr1Eman A. Rabie2Naglaa O. Mostafa3Sonia A. Habib4Ghada Y. El‐Kamah5Molecular Genetics and Enzymology Department Human Genetics and Genome Research Division (HGGR)National Research Centre (NRC) Cairo EgyptMedical Molecular Genetics HGGRNRC Cairo EgyptMedical Molecular Genetics HGGRNRC Cairo EgyptDepartment of Hematology Pediatric HospitalCairo University Cairo EgyptDepartment of Pediatrics Medical Division NRC Cairo EgyptClinical Genetics Department HGGRNRC Cairo EgyptAbstract Background Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (F8) deficiency. F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational patterns. This study aims to identify F8 gene mutations among Egyptian HA patients. Methods DNA samples from 60 HA patients were screened for int22 and int1 rearrangements using simplified inverse shifting PCR (IS‐PCR) followed by exon 14 sequencing. Also, four uncharacterized patients were studied by targeted exome sequencing. Results In 33.3% of the studied patients, we identified three int22 rearrangements, three exon 14 mutations (two frameshift; one novel (NM_000132.3:c.2734_2735delAA, p.(N912Ffs*6)), a second reported mutation (NM_000132.3:c.3091_3094delAGAA, p.(K1031Lfs*9)), and one nonsense mutation (NM_000132.3:c.2440C>T, p.(R814*)). All identified mutations were detected in patients with severe HA phenotype. Targeted exome sequencing could not detect any known pathogenic variants. Conclusion Intron 22 rearrangement and exon 14 mutations correlate with most severe hemophilia A Egyptian patients.https://doi.org/10.1002/mgg3.1575FVIII proteinhemophilia Ahuman F8 genemutationnonsense |
| spellingShingle | Rehab M. Mosaad Khalda S. Amr Eman A. Rabie Naglaa O. Mostafa Sonia A. Habib Ghada Y. El‐Kamah Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients Molecular Genetics & Genomic Medicine FVIII protein hemophilia A human F8 gene mutation nonsense |
| title | Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients |
| title_full | Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients |
| title_fullStr | Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients |
| title_full_unstemmed | Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients |
| title_short | Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients |
| title_sort | genomic alterations in the f8 gene correlating with severe hemophilia a in egyptian patients |
| topic | FVIII protein hemophilia A human F8 gene mutation nonsense |
| url | https://doi.org/10.1002/mgg3.1575 |
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