Clinical and functional characterization of p.Lys322stop variant in the SERPINC1 gene causing severe thrombophilia.

ABSTRACT:

Background

Identification of mutations in the SERPINC1 has illuminated the intricate pathways underlying antithrombin (AT) deficiency. Our group identified a variation in the SERPINC1 gene (c.964 A > T, p.Lys322stop) and further investigated the mechanism of this variant causing AT deficiency.

Methods

Multiple in silico tools were utilized to predict the conservation of mutations and their impact on the AT structure. The coagulation state was evaluated using the thrombin generation assay. Recombinant AT was overexpressed in HEK293T cells. Intracellular kinetics and extracellular secretion of recombinant AT-K322* were scrutinized by RT-qPCR, Western blotting, ELISA, and immunocytofluorescence.

Results

Analysis of conservation in silico indicated 43 out of the 143 amino

SUBMITTER: Zhang H 

PROVIDER: S-EPMC11662841 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature