Figure 2.
Contribution of CRM in hemophilia B and FIX variant hot spots associated with qualitative defects. (A) Relation between FIX:Act and FIX:Ag reported for patients with hemophilia B harboring a missense mutation (n = 663 cases with FIX:Act and FIX:Ag data available). Each dot represents 1 hemophilia B case, and the colored rectangles indicate the disease classification based on FIX:Act (blue = mild hemophilia, yellow = moderate hemophilia, and red = severe hemophilia). Cases with CRM+ with FIX:Ag ≥40 U/dL (dashed line) were indicated by the dashed line and colored rectangles of disease severity. (B) Distribution of reported FIX:Ag levels in patients with mild (n = 171), moderate (n = 244), or severe (n = 248) hemophilia B based on their FIX activity levels. Median and interquartile range of FIX:Ag and proportion (%) of patients with FIX:Ag ≥40 U/dL are provided per severity subclass. (C) Skyline of variant location hot spots associated with qualitative defects in FIX. For hemophilia B cases with FIX:Act and FIX:Ag levels available (n = 663), the FIX:Ag/FIX:Act ratio was determined to unveil variants associated with qualitative defects. Each dot represents an individual patient case, disease severity is indicated by color, and cases are arranged by variant location within FIX. (D) Hemophilia B CRM+ cases with residual systemic levels of FIX:Ag ≥40% were selected (n = 303), and the median FIX:Ag/FIX:Act was provided per variant location. Data are colored by the domains signal peptide (SP), propeptide (PP), Gla domain (Gla), EGF-like domains (EGF-1 and -2), linker sequence, activation peptide (AP), and serine protease domain. Residues located in the Gla and EGF-1 domains involved in calcium ion positioning are marked ( | ), and proteolytic cleavage sites are visualized by dashed lines. All data are based on the EAHAD F9 Variant Database (accessed on 6 May 2024).

Contribution of CRM in hemophilia B and FIX variant hot spots associated with qualitative defects. (A) Relation between FIX:Act and FIX:Ag reported for patients with hemophilia B harboring a missense mutation (n = 663 cases with FIX:Act and FIX:Ag data available). Each dot represents 1 hemophilia B case, and the colored rectangles indicate the disease classification based on FIX:Act (blue = mild hemophilia, yellow = moderate hemophilia, and red = severe hemophilia). Cases with CRM+ with FIX:Ag ≥40 U/dL (dashed line) were indicated by the dashed line and colored rectangles of disease severity. (B) Distribution of reported FIX:Ag levels in patients with mild (n = 171), moderate (n = 244), or severe (n = 248) hemophilia B based on their FIX activity levels. Median and interquartile range of FIX:Ag and proportion (%) of patients with FIX:Ag ≥40 U/dL are provided per severity subclass. (C) Skyline of variant location hot spots associated with qualitative defects in FIX. For hemophilia B cases with FIX:Act and FIX:Ag levels available (n = 663), the FIX:Ag/FIX:Act ratio was determined to unveil variants associated with qualitative defects. Each dot represents an individual patient case, disease severity is indicated by color, and cases are arranged by variant location within FIX. (D) Hemophilia B CRM+ cases with residual systemic levels of FIX:Ag ≥40% were selected (n = 303), and the median FIX:Ag/FIX:Act was provided per variant location. Data are colored by the domains signal peptide (SP), propeptide (PP), Gla domain (Gla), EGF-like domains (EGF-1 and -2), linker sequence, activation peptide (AP), and serine protease domain. Residues located in the Gla and EGF-1 domains involved in calcium ion positioning are marked ( | ), and proteolytic cleavage sites are visualized by dashed lines. All data are based on the EAHAD F9 Variant Database (accessed on 6 May 2024).

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal