Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov 23:14:445-454.
doi: 10.2147/TACG.S288256. eCollection 2021.

The Clinical Genetics of Hemophilia B (Factor IX Deficiency)

Connie H Miller  1   2
Affiliations
Review

The Clinical Genetics of Hemophilia B (Factor IX Deficiency)

Connie H Miller. Appl Clin Genet. .

Abstract

Hemophilia B (HB) is a bleeding disorder caused by deficiency of or defect in blood coagulation factor IX (FIX) inherited in an X-linked manner. It results from one of over 1000 known pathogenic variants in the FIX gene, F9; missense and frameshift changes predominate. Although primarily males are affected with HB, heterozygous females may have excessive bleeding due to random or non-random X chromosome inactivation; in addition, homozygous, compound heterozygous, and hemizygous females have been reported. Somatic and germinal mosaicism for F9 variants has been observed. Development of antibodies to FIX treatment products (inhibitors) is rare and related to the type of causative variant present. Treatment is with products produced by recombinant DNA technology, and gene therapy is in clinical trials. Genetic counseling with up-to-date information is warranted for heterozygotes, potential heterozygotes, and men and women affected with HB.

Keywords: factor IX; genetics; hematology; hemophilia B.

PubMed Disclaimer

Conflict of interest statement

The author reports no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Diagram of factor IX (FIX) gene and protein structure. (A) FIX gene (F9). (B). FIX protein showing amino acids numbered by Human Genome Variation Society nomenclature. (C). Activated FIX (FIXa). Domains include signal peptide (Signal), propeptide (Pro), gamma-carboxyglutamic acid (Gla), hydrophobic segment (H), epidermal growth factor (EGF) 1, EGF 2, linker peptide (L), activation peptide (Act), serine protease.
Figure 2
Figure 2
Distributions of factor IX activity in women heterozygous for variants causing hemophilia B (heterozygotes) and for women not having variants causing hemophilia (controls). Reproduced with permission from Miller CH, Bean CJ. Genetic causes of haemophilia in women and girls. Haemophilia. 2020;27(2):e164–e179. © Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
See this image and copyright information in PMC

References

    1. Castaman G, Matino D. Hemophilia A and B: molecular and clinical similarities and differences. Haematologica. 2019;104(9):1702–1709. doi: 10.3324/haematol.2019.221093 - DOI - PMC - PubMed
    1. Choo KH, Gould KG, Rees DJG, Brownlee GG. Molecular cloning of the gene for human anti-haemophilic factor IX. Nature. 1982;299(5879):178–180. doi: 10.1038/299178a0 - DOI - PubMed
    1. Kurachi K, Davie EW. Isolation and characterization of a cDNA coding for human factor IX. Proc Natl Acad Sci USA. 1982;79(21I):6461–6464. doi: 10.1073/pnas.79.21.6461 - DOI - PMC - PubMed
    1. Rallapalli PM, Kemball-Cook G, Tuddenham EG, Gomez K, Perkins SJ. An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B. J Thromb Haemost. 2013;11(7):1329–1340. doi: 10.1111/jth.12276 - DOI - PubMed
    1. Li T, Miller CH, Payne AB, Hooper WC. The CDC Hemophilia B mutation project mutation list: a new online resource. Mol Genet Genomic Med. 2013;1(4):238–245. doi: 10.1002/mgg3.30 - DOI - PMC - PubMed