Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations
| Autor: | Fahri Şahin, Ekrem Unal, Birol Baytan, Fatma Burcu Belen, Ferda Ozkinay, Yeşim Oymak, Vildan Çulha, Gülen Tüysüz, Adalet Meral Güneş, Kaan Kavakli, Bilçağ Akgün, Melike Sezgin Evim, Namik Ozbek, Alphan Kupesiz, Tahir Atik, Esra Isik, Hüseyin Onay, Moharram Shamsali, Can Balkan, Ebru Yılmaz Keskin, Zafer Salcioglu, Canan Albayrak, Tuba Nur Tahtakesen Güçer |
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| Přispěvatelé: | Ege Üniversitesi |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:Internal medicine Turkey Population 030204 cardiovascular system & hematology Gene mutation Hemophilia A 0-Belirlenecek 03 medical and health sciences 0302 clinical medicine F8 gene Pediatric genetics Genotype Medicine education lcsh:RC31-1245 Gene Genetics education.field_of_study business.industry lcsh:RC633-647.5 Inhibitors Point mutation Intron Hematology lcsh:Diseases of the blood and blood-forming organs 030104 developmental biology Mutation (genetic algorithm) Mutation business Intron 22 inversion Research Article |
| Zdroj: | Turkish Journal of Hematology Turkish Journal of Hematology, Vol 37, Iss 3, Pp 145-153 (2020) |
| ISSN: | 1308-5263 1300-7777 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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