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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...

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Autores principales: Atik, Tahir, Işık, Esra, Onay, Hüseyin, Akgün, Bilçağ, Shamsali, Moharram, Kavaklo, Kaan, Evim, Melike, Tüysüz, Gülen, Özbek, Namık Yaşar, Şahin, Fahri, Salcıoğlu, Zafer, Albayrak, Canan, Oymak, Yeşim, Ünal, Ekrem, Belen, Fatma Burcu, Yılmaz Keskin, Ebru, Balkan, Can, Baytan, Birol, Küpesiz, Alphan, Culha, Vildan, Tahtakesen Güçer, Tuba Nur, Güneş, Adalet Meral, Özkınay, Ferda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Galenos Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463214/
https://www.ncbi.nlm.nih.gov/pubmed/32026663
http://dx.doi.org/10.4274/tjh.galenos.2020.2019.0262
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author Atik, Tahir
Işık, Esra
Onay, Hüseyin
Akgün, Bilçağ
Shamsali, Moharram
Kavaklo, Kaan
Evim, Melike
Tüysüz, Gülen
Özbek, Namık Yaşar
Şahin, Fahri
Salcıoğlu, Zafer
Albayrak, Canan
Oymak, Yeşim
Ünal, Ekrem
Belen, Fatma Burcu
Yılmaz Keskin, Ebru
Balkan, Can
Baytan, Birol
Küpesiz, Alphan
Culha, Vildan
Tahtakesen Güçer, Tuba Nur
Güneş, Adalet Meral
Özkınay, Ferda
author_facet Atik, Tahir
Işık, Esra
Onay, Hüseyin
Akgün, Bilçağ
Shamsali, Moharram
Kavaklo, Kaan
Evim, Melike
Tüysüz, Gülen
Özbek, Namık Yaşar
Şahin, Fahri
Salcıoğlu, Zafer
Albayrak, Canan
Oymak, Yeşim
Ünal, Ekrem
Belen, Fatma Burcu
Yılmaz Keskin, Ebru
Balkan, Can
Baytan, Birol
Küpesiz, Alphan
Culha, Vildan
Tahtakesen Güçer, Tuba Nur
Güneş, Adalet Meral
Özkınay, Ferda
author_sort Atik, Tahir
collection PubMed
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.
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spelling pubmed-74632142020-09-16 Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations Atik, Tahir Işık, Esra Onay, Hüseyin Akgün, Bilçağ Shamsali, Moharram Kavaklo, Kaan Evim, Melike Tüysüz, Gülen Özbek, Namık Yaşar Şahin, Fahri Salcıoğlu, Zafer Albayrak, Canan Oymak, Yeşim Ünal, Ekrem Belen, Fatma Burcu Yılmaz Keskin, Ebru Balkan, Can Baytan, Birol Küpesiz, Alphan Culha, Vildan Tahtakesen Güçer, Tuba Nur Güneş, Adalet Meral Özkınay, Ferda Turk J Haematol Research Article 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. Galenos Publishing 2020-09 2020-08-28 /pmc/articles/PMC7463214/ /pubmed/32026663 http://dx.doi.org/10.4274/tjh.galenos.2020.2019.0262 Text en © Copyright 2020 by Turkish Society of Hematology / Turkish Journal of Hematology, Published by Galenos Publishing House. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Atik, Tahir
Işık, Esra
Onay, Hüseyin
Akgün, Bilçağ
Shamsali, Moharram
Kavaklo, Kaan
Evim, Melike
Tüysüz, Gülen
Özbek, Namık Yaşar
Şahin, Fahri
Salcıoğlu, Zafer
Albayrak, Canan
Oymak, Yeşim
Ünal, Ekrem
Belen, Fatma Burcu
Yılmaz Keskin, Ebru
Balkan, Can
Baytan, Birol
Küpesiz, Alphan
Culha, Vildan
Tahtakesen Güçer, Tuba Nur
Güneş, Adalet Meral
Özkınay, Ferda
Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations
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 Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463214/
https://www.ncbi.nlm.nih.gov/pubmed/32026663
http://dx.doi.org/10.4274/tjh.galenos.2020.2019.0262
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