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CC BY 4.0 · Glob Med Genet 2023; 10(03): 247-262
DOI: 10.1055/s-0043-1774322
Original Article

Molecular Diagnosis of Hemophilia A and Pathogenesis of Novel F8 Variants in Shanxi, China

Xialin Zhang
1   Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
2   Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Kun Chen
2   Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Sicheng Bian
3   Department of Medicine, Case Western Reserve University, Cleveland, Ohio
,
Gang Wang
4   Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
,
Xiuyu Qin
4   Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
,
Ruijuan Zhang
1   Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
2   Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Linhua Yang
4   Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
› Institutsangaben Funding This research was funded by Shanxi Provincial Key Research and Development Project (No. 201903D321133), the Basic Research Project of Shanxi Province (No. 20210302124037, No. 20210302123295), and Shanxi Bethune Talent Foundation Project (No. 2021RC017, No. 2021RC038).
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Abstract

The aim of this study was to perform a molecular diagnosis of hemophilia A (HA) among patients in the Shanxi Province of China. Fifty-two HA patients were tested, including IVS22 (31 samples), IVS1 (3 samples), missense (11 samples), nonsense (3 samples), and 4 cases of frameshift (2 cases of deletion, 1 case of insertion, 1 case of single-base duplication). With the exception of the single-base G duplication variant (p.Ile1213Asnfs*28), this was the hotspot variant reported by research groups at an early stage. The remaining variants were found, for the first time, in the region. The missense variants p.Cys172Ser, p.Tyr404Ser, p.Asp1903Gly, and p.Ser2284Asn, the deletion variant p.Leu2249fs*9, and the insertion variant p.Pro2319fs*97 were novel variants. The application of next-generation sequencing (NGS) molecular diagnosis enriched the variant spectrum of HA, which is greatly significant for individualized genetic counseling, clinical diagnosis, and treatment. NGS and a variety of bioinformatics prediction methods can further analyze the impact of genetic variation on protein structure or function and lay the foundation to reveal the molecular pathogenic mechanism of novel variants.

Keywords

hemophilia A - molecular diagnosis - pathogenic mechanism - novel variants


Publikationsverlauf

Artikel online veröffentlicht:
13. September 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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