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A Novel Deletion Mutation of the F8 Gene for Hemophilia A

Background: Hemophilia A (HA) is an X-linked recessive blood coagulation disorder caused by a variety of abnormalities in F8 gene, resulting in the absence of impaired molecule production of factor VIII (FVIII) in the plasma. The genetic testing of the F8 gene encoding FVIII is used for confirmation...

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Autores principales: Wang, Jingwei, Gu, Jian, Chen, Hongbing, Wu, Qian, Xiong, Liang, Qiao, Bin, Zhang, Yan, Xiao, Hongjun, Tong, Yongqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689134/
https://www.ncbi.nlm.nih.gov/pubmed/36428936
http://dx.doi.org/10.3390/diagnostics12112876
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author Wang, Jingwei
Gu, Jian
Chen, Hongbing
Wu, Qian
Xiong, Liang
Qiao, Bin
Zhang, Yan
Xiao, Hongjun
Tong, Yongqing
author_facet Wang, Jingwei
Gu, Jian
Chen, Hongbing
Wu, Qian
Xiong, Liang
Qiao, Bin
Zhang, Yan
Xiao, Hongjun
Tong, Yongqing
author_sort Wang, Jingwei
collection PubMed
description Background: Hemophilia A (HA) is an X-linked recessive blood coagulation disorder caused by a variety of abnormalities in F8 gene, resulting in the absence of impaired molecule production of factor VIII (FVIII) in the plasma. The genetic testing of the F8 gene encoding FVIII is used for confirmation of HA diagnosis, which significantly reduced serious complications of this disease and, ultimately, increased life expectancy. Methods: Sanger sequencing was performed in F8 gene exons of the suspected patients with blood coagulation-related indicators. Results: A novel F8 indel variant c.6343delC, p.Leu2115SerfsTer28 in exon 22 of the F8 gene was identified in the suspected families. The infant with this novel variant appeared the symptom of minor bleeding and oral cavity bleeding, and decreased activity of FVIII, which is consistent with that of F8 deleterious variants. The 3’D protein structural analysis of the novel variant shows a change in FVIII protein stability, which may be responsible for the pathogenesis of HA. Conclusions: A novel deleterious variant was identified in our case, which expands the F8 variants spectrum. Our result is helpful for HA diagnosis and benefits carrier detection and prenatal diagnosis. Our study also reveals that mutation screening of the F8 gene should be necessary for HA suspected patients.
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spelling pubmed-96891342022-11-25 A Novel Deletion Mutation of the F8 Gene for Hemophilia A Wang, Jingwei Gu, Jian Chen, Hongbing Wu, Qian Xiong, Liang Qiao, Bin Zhang, Yan Xiao, Hongjun Tong, Yongqing Diagnostics (Basel) Case Report Background: Hemophilia A (HA) is an X-linked recessive blood coagulation disorder caused by a variety of abnormalities in F8 gene, resulting in the absence of impaired molecule production of factor VIII (FVIII) in the plasma. The genetic testing of the F8 gene encoding FVIII is used for confirmation of HA diagnosis, which significantly reduced serious complications of this disease and, ultimately, increased life expectancy. Methods: Sanger sequencing was performed in F8 gene exons of the suspected patients with blood coagulation-related indicators. Results: A novel F8 indel variant c.6343delC, p.Leu2115SerfsTer28 in exon 22 of the F8 gene was identified in the suspected families. The infant with this novel variant appeared the symptom of minor bleeding and oral cavity bleeding, and decreased activity of FVIII, which is consistent with that of F8 deleterious variants. The 3’D protein structural analysis of the novel variant shows a change in FVIII protein stability, which may be responsible for the pathogenesis of HA. Conclusions: A novel deleterious variant was identified in our case, which expands the F8 variants spectrum. Our result is helpful for HA diagnosis and benefits carrier detection and prenatal diagnosis. Our study also reveals that mutation screening of the F8 gene should be necessary for HA suspected patients. MDPI 2022-11-21 /pmc/articles/PMC9689134/ /pubmed/36428936 http://dx.doi.org/10.3390/diagnostics12112876 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Wang, Jingwei
Gu, Jian
Chen, Hongbing
Wu, Qian
Xiong, Liang
Qiao, Bin
Zhang, Yan
Xiao, Hongjun
Tong, Yongqing
A Novel Deletion Mutation of the F8 Gene for Hemophilia A
title A Novel Deletion Mutation of the F8 Gene for Hemophilia A
title_full A Novel Deletion Mutation of the F8 Gene for Hemophilia A
title_fullStr A Novel Deletion Mutation of the F8 Gene for Hemophilia A
title_full_unstemmed A Novel Deletion Mutation of the F8 Gene for Hemophilia A
title_short A Novel Deletion Mutation of the F8 Gene for Hemophilia A
title_sort novel deletion mutation of the f8 gene for hemophilia a
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689134/
https://www.ncbi.nlm.nih.gov/pubmed/36428936
http://dx.doi.org/10.3390/diagnostics12112876
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