F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes.

ABSTRACT:

Background

Circulating dysfunctional factor IX (FIX) might modulate distribution of infused FIX in hemophilia B (HB) patients. Recurrent substitutions at FIX activation sites (R191-R226, >300 patients) are associated with variable FIX activity and antigen (FIXag) levels.

Objectives

To investigate the (1) expression of a complete panel of missense mutations at FIX activation sites and (2) contribution of F9 genotypes on the FIX pharmacokinetics (PK).

Methods

We checked FIX activity and antigen and activity assays in plasma and after recombinant expression of FIX variants and performed an analysis of infused FIX PK parameters in patients (n = 30), mostly enrolled in the F9 Genotype and PK HB Italian Study (GePKHIS; EudraCT ID2017-003902-42).

Results

The variable

SUBMITTER: Branchini A 

PROVIDER: S-EPMC9298354 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature