TY  - JOUR
TI  - Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations
AB  - 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.
AU  - Oymak, Yeşim
AU  - SHAMSALI, Moharram
AU  - UNAL, Ekrem
AU  - Akgun, Bilcag
AU  - sezgin evim, melike
AU  - BAYTAN, Birol
AU  - Kupesiz, Osman Alphan
AU  - Ozkinay, Ferda
AU  - KESKİN, Ebru Yılmaz
AU  - BALKAN, CAN
AU  - Sahin, Fahri
AU  - Onay, Huseyin
AU  - belen, fatma burcu
AU  - KAVAKLO, Kaan
AU  - Şalcıoğlu, Zafer
AU  - culha, vildan
AU  - Tüysüz, Gülen
AU  - ALBAYRAK, Canan Uçar
AU  - ozbek, namik yasar
AU  - isik, esra
AU  - Tahtakesen, Tuba Nur
AU  - ATIK, TAHIR
DO  - 10.4274/tjh.galenos.2020.2019.0262
PY  - 2020
JO  - Turkish Journal of Hematology
VL  - 37
IS  - 3
SN  - 1300-7777
SP  - 145
EP  - 153
DB  - TRDizin
UR  - http://search/yayin/detay/380846
ER  -