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 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.

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APA	ATIK T, isik e, Akgun B, Ozkinay F, Onay H, SHAMSALI M, KAVAKLO K, BALKAN C, sezgin evim m, BAYTAN B, Tüysüz G, Kupesiz O, ozbek n, culha v, Sahin F, Şalcıoğlu Z, Tahtakesen T, ALBAYRAK C, Oymak Y, UNAL E, belen f, KESKİN E (2020). Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. , 145 - 153. 10.4274/tjh.galenos.2020.2019.0262
Chicago	ATIK TAHIR,isik esra,Akgun Bilcag,Ozkinay Ferda,Onay Huseyin,SHAMSALI Moharram,KAVAKLO Kaan,BALKAN CAN,sezgin evim melike,BAYTAN Birol,Tüysüz Gülen,Kupesiz Osman Alphan,ozbek namik yasar,culha vildan,Sahin Fahri,Şalcıoğlu Zafer,Tahtakesen Tuba Nur,ALBAYRAK Canan Uçar,Oymak Yeşim,UNAL Ekrem,belen fatma burcu,KESKİN Ebru Yılmaz Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. (2020): 145 - 153. 10.4274/tjh.galenos.2020.2019.0262
MLA	ATIK TAHIR,isik esra,Akgun Bilcag,Ozkinay Ferda,Onay Huseyin,SHAMSALI Moharram,KAVAKLO Kaan,BALKAN CAN,sezgin evim melike,BAYTAN Birol,Tüysüz Gülen,Kupesiz Osman Alphan,ozbek namik yasar,culha vildan,Sahin Fahri,Şalcıoğlu Zafer,Tahtakesen Tuba Nur,ALBAYRAK Canan Uçar,Oymak Yeşim,UNAL Ekrem,belen fatma burcu,KESKİN Ebru Yılmaz Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. , 2020, ss.145 - 153. 10.4274/tjh.galenos.2020.2019.0262
AMA	ATIK T,isik e,Akgun B,Ozkinay F,Onay H,SHAMSALI M,KAVAKLO K,BALKAN C,sezgin evim m,BAYTAN B,Tüysüz G,Kupesiz O,ozbek n,culha v,Sahin F,Şalcıoğlu Z,Tahtakesen T,ALBAYRAK C,Oymak Y,UNAL E,belen f,KESKİN E Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. . 2020; 145 - 153. 10.4274/tjh.galenos.2020.2019.0262
Vancouver	ATIK T,isik e,Akgun B,Ozkinay F,Onay H,SHAMSALI M,KAVAKLO K,BALKAN C,sezgin evim m,BAYTAN B,Tüysüz G,Kupesiz O,ozbek n,culha v,Sahin F,Şalcıoğlu Z,Tahtakesen T,ALBAYRAK C,Oymak Y,UNAL E,belen f,KESKİN E Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. . 2020; 145 - 153. 10.4274/tjh.galenos.2020.2019.0262
IEEE	ATIK T,isik e,Akgun B,Ozkinay F,Onay H,SHAMSALI M,KAVAKLO K,BALKAN C,sezgin evim m,BAYTAN B,Tüysüz G,Kupesiz O,ozbek n,culha v,Sahin F,Şalcıoğlu Z,Tahtakesen T,ALBAYRAK C,Oymak Y,UNAL E,belen f,KESKİN E "Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations." , ss.145 - 153, 2020. 10.4274/tjh.galenos.2020.2019.0262
ISNAD	ATIK, TAHIR vd. "Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations". (2020), 145-153. https://doi.org/10.4274/tjh.galenos.2020.2019.0262

APA	ATIK T, isik e, Akgun B, Ozkinay F, Onay H, SHAMSALI M, KAVAKLO K, BALKAN C, sezgin evim m, BAYTAN B, Tüysüz G, Kupesiz O, ozbek n, culha v, Sahin F, Şalcıoğlu Z, Tahtakesen T, ALBAYRAK C, Oymak Y, UNAL E, belen f, KESKİN E (2020). Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. Turkish Journal of Hematology, 37(3), 145 - 153. 10.4274/tjh.galenos.2020.2019.0262
Chicago	ATIK TAHIR,isik esra,Akgun Bilcag,Ozkinay Ferda,Onay Huseyin,SHAMSALI Moharram,KAVAKLO Kaan,BALKAN CAN,sezgin evim melike,BAYTAN Birol,Tüysüz Gülen,Kupesiz Osman Alphan,ozbek namik yasar,culha vildan,Sahin Fahri,Şalcıoğlu Zafer,Tahtakesen Tuba Nur,ALBAYRAK Canan Uçar,Oymak Yeşim,UNAL Ekrem,belen fatma burcu,KESKİN Ebru Yılmaz Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. Turkish Journal of Hematology 37, no.3 (2020): 145 - 153. 10.4274/tjh.galenos.2020.2019.0262
MLA	ATIK TAHIR,isik esra,Akgun Bilcag,Ozkinay Ferda,Onay Huseyin,SHAMSALI Moharram,KAVAKLO Kaan,BALKAN CAN,sezgin evim melike,BAYTAN Birol,Tüysüz Gülen,Kupesiz Osman Alphan,ozbek namik yasar,culha vildan,Sahin Fahri,Şalcıoğlu Zafer,Tahtakesen Tuba Nur,ALBAYRAK Canan Uçar,Oymak Yeşim,UNAL Ekrem,belen fatma burcu,KESKİN Ebru Yılmaz Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. Turkish Journal of Hematology, vol.37, no.3, 2020, ss.145 - 153. 10.4274/tjh.galenos.2020.2019.0262
AMA	ATIK T,isik e,Akgun B,Ozkinay F,Onay H,SHAMSALI M,KAVAKLO K,BALKAN C,sezgin evim m,BAYTAN B,Tüysüz G,Kupesiz O,ozbek n,culha v,Sahin F,Şalcıoğlu Z,Tahtakesen T,ALBAYRAK C,Oymak Y,UNAL E,belen f,KESKİN E Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. Turkish Journal of Hematology. 2020; 37(3): 145 - 153. 10.4274/tjh.galenos.2020.2019.0262
Vancouver	ATIK T,isik e,Akgun B,Ozkinay F,Onay H,SHAMSALI M,KAVAKLO K,BALKAN C,sezgin evim m,BAYTAN B,Tüysüz G,Kupesiz O,ozbek n,culha v,Sahin F,Şalcıoğlu Z,Tahtakesen T,ALBAYRAK C,Oymak Y,UNAL E,belen f,KESKİN E Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations. Turkish Journal of Hematology. 2020; 37(3): 145 - 153. 10.4274/tjh.galenos.2020.2019.0262
IEEE	ATIK T,isik e,Akgun B,Ozkinay F,Onay H,SHAMSALI M,KAVAKLO K,BALKAN C,sezgin evim m,BAYTAN B,Tüysüz G,Kupesiz O,ozbek n,culha v,Sahin F,Şalcıoğlu Z,Tahtakesen T,ALBAYRAK C,Oymak Y,UNAL E,belen f,KESKİN E "Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations." Turkish Journal of Hematology, 37, ss.145 - 153, 2020. 10.4274/tjh.galenos.2020.2019.0262
ISNAD	ATIK, TAHIR vd. "Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations". Turkish Journal of Hematology 37/3 (2020), 145-153. https://doi.org/10.4274/tjh.galenos.2020.2019.0262