Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations
Objective: Hemophilia A (HA) is the most severe X-linked inherited bleeding disorder caused by hemizygous mutations in the factor 8 (F8) gene. The aim of this study is to determine the mutation spectrum of the F8 gene in a large HA cohort from Turkey, and then to establish a phenotype-genotype corre...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Galenos Publishing House
2020-08-01
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| Series: | Turkish Journal of Hematology |
| Subjects: | |
| Online Access: | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-65625 |
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| author | Tahir Atik Esra Işık Hüseyin Onay Bilçağ Akgün Moharram Shamsali Kaan Kavaklo Melike Evim Gülen Tüysüz Namık Yaşar Özbek Fahri Şahin Zafer Salcıoğlu Canan Albayrak Yeşim Oymak Ekrem Ünal Fatma Burcu Belen Ebru Yılmaz Keskin Can Balkan Birol Baytan Alphan Küpesiz Vildan Culha Tuba Nur Tahtakesen Adalet Meral Güneş Ferda Özkınay |
| author_facet | Tahir Atik Esra Işık Hüseyin Onay Bilçağ Akgün Moharram Shamsali Kaan Kavaklo Melike Evim Gülen Tüysüz Namık Yaşar Özbek Fahri Şahin Zafer Salcıoğlu Canan Albayrak Yeşim Oymak Ekrem Ünal Fatma Burcu Belen Ebru Yılmaz Keskin Can Balkan Birol Baytan Alphan Küpesiz Vildan Culha Tuba Nur Tahtakesen Adalet Meral Güneş Ferda Özkınay |
| author_sort | Tahir Atik |
| collection | DOAJ |
| description | Objective: Hemophilia A (HA) is the most severe X-linked inherited bleeding disorder caused by hemizygous mutations in the factor 8 (F8) gene. The aim of this study is to determine the mutation spectrum of the F8 gene in a large HA cohort from Turkey, and then to establish a phenotype-genotype correlation. Materials and Methods: All HA cases (270 patients) analyzed molecularly in the Ege University Pediatric Genetics Molecular Laboratory between March 2017 and March 2018 were included in this study. To identify intron 22 inversion (Inv22), intron 1 inversion (Inv1), small deletion/insertions, and point mutations, molecular analyses of F8 were performed using a sequential application of molecular techniques. Results: The mutation detection success rate was 95.2%. Positive Inv22 was found in 106 patients (39.3%), Inv1 was found in 4 patients (1.5%), and 106 different disease-causing sequence variants were identified in 137 patients (50.6%). In 10 patients (3.7%), amplification failures involving one or more exonic regions, considered to be large intragenic deletions, were identified. Of 106 different F8 mutations, 36 were novel. The relationship between F8 genotype and inhibitor development was considered significant. Conclusion: A high mutation detection rate was achieved via the broad molecular techniques applied in this study, including 36 novel mutations. With regard to mutation types, mutation distribution and their impact on clinical severity and inhibitor development were found to be similar to those previously reported in other hemophilia population studies. |
| first_indexed | 2024-04-10T11:55:55Z |
| format | Article |
| id | doaj.art-739b1796010f4465a28442c9b6243a1b |
| institution | Directory Open Access Journal |
| issn | 1308-5263 |
| language | English |
| last_indexed | 2024-04-10T11:55:55Z |
| publishDate | 2020-08-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Turkish Journal of Hematology |
| spelling | doaj.art-739b1796010f4465a28442c9b6243a1b2023-02-15T16:16:48ZengGalenos Publishing HouseTurkish Journal of Hematology1308-52632020-08-0137314515310.4274/tjh.galenos.2020.2019.0262TJH-65625Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel MutationsTahir Atik0Esra Işık1Hüseyin Onay2Bilçağ Akgün3Moharram Shamsali4Kaan Kavaklo5Melike Evim6Gülen Tüysüz7Namık Yaşar Özbek8Fahri Şahin9Zafer Salcıoğlu10Canan Albayrak11Yeşim Oymak12Ekrem Ünal13Fatma Burcu Belen14Ebru Yılmaz Keskin15Can Balkan16Birol Baytan17Alphan Küpesiz18Vildan Culha19Tuba Nur Tahtakesen20Adalet Meral Güneş21Ferda Özkınay22Ege University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Genetics, İzmir, TurkeyEge University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Genetics, İzmir, TurkeyEge University Faculty of Medicine, Department of Medical Genetics, İzmir, TurkeyEge University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Genetics, İzmir, TurkeyEge University Institute of Health Sciences, Division of Health Bioinformatics, İzmir, TurkeyEge University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, İzmir, TurkeyUludağ University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Bursa, TurkeyAkdeniz University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Antalya, TurkeyUniversity of Health Sciences Turkey Ankara Pediatric Hematology Oncology Training and Research Hospital, Clinic of Pediatric Hematology, Ankara, TurkeyEge University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, İzmir, Turkeyİstanbul Kanuni Sultan Süleyman Training and Research Hospital, Clinic of Pediatric Hematology and Oncology, İstanbul, TurkeyOndokuz Mayıs University Faculty of Medicine, Department of Pediatric Hematology and Oncology, Samsun, TurkeyDr. Behcet Uz Children's Hospital, Division of Pediatric Hematology, İzmir, TurkeyErciyes University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Kayseri, TurkeyKatip Çelebi University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, İzmir, TurkeySüleyman Demirel University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Isparta, TurkeyEge University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, İzmir, TurkeyUludağ University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Bursa, TurkeyAkdeniz University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Antalya, TurkeyUniversity of Health Sciences Turkey Ankara Pediatric Hematology Oncology Training and Research Hospital, Clinic of Pediatric Hematology, Ankara, Turkeyİstanbul Kanuni Sultan Süleyman Training and Research Hospital, Clinic of Pediatric Hematology and Oncology, İstanbul, TurkeyUludağ University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Bursa, TurkeyEge University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Genetics, İzmir, TurkeyObjective: Hemophilia A (HA) is the most severe X-linked inherited bleeding disorder caused by hemizygous mutations in the factor 8 (F8) gene. The aim of this study is to determine the mutation spectrum of the F8 gene in a large HA cohort from Turkey, and then to establish a phenotype-genotype correlation. Materials and Methods: All HA cases (270 patients) analyzed molecularly in the Ege University Pediatric Genetics Molecular Laboratory between March 2017 and March 2018 were included in this study. To identify intron 22 inversion (Inv22), intron 1 inversion (Inv1), small deletion/insertions, and point mutations, molecular analyses of F8 were performed using a sequential application of molecular techniques. Results: The mutation detection success rate was 95.2%. Positive Inv22 was found in 106 patients (39.3%), Inv1 was found in 4 patients (1.5%), and 106 different disease-causing sequence variants were identified in 137 patients (50.6%). In 10 patients (3.7%), amplification failures involving one or more exonic regions, considered to be large intragenic deletions, were identified. Of 106 different F8 mutations, 36 were novel. The relationship between F8 genotype and inhibitor development was considered significant. Conclusion: A high mutation detection rate was achieved via the broad molecular techniques applied in this study, including 36 novel mutations. With regard to mutation types, mutation distribution and their impact on clinical severity and inhibitor development were found to be similar to those previously reported in other hemophilia population studies.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-65625hemophilia af8 genemutationinhibitorsintron 22 inversionturkey |
| spellingShingle | Tahir Atik Esra Işık Hüseyin Onay Bilçağ Akgün Moharram Shamsali Kaan Kavaklo Melike Evim Gülen Tüysüz Namık Yaşar Özbek Fahri Şahin Zafer Salcıoğlu Canan Albayrak Yeşim Oymak Ekrem Ünal Fatma Burcu Belen Ebru Yılmaz Keskin Can Balkan Birol Baytan Alphan Küpesiz Vildan Culha Tuba Nur Tahtakesen Adalet Meral Güneş Ferda Özkınay Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations Turkish Journal of Hematology hemophilia a f8 gene mutation inhibitors intron 22 inversion turkey |
| title | Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations |
| title_full | Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations |
| title_fullStr | Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations |
| title_full_unstemmed | Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations |
| title_short | Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations |
| title_sort | factor 8 gene mutation spectrum of 270 patients with hemophilia a identification of 36 novel mutations |
| topic | hemophilia a f8 gene mutation inhibitors intron 22 inversion turkey |
| url | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-65625 |
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