ABSTRACT Background Congenital factor XIII (FXIII) deficiency is an extremely rare autosomal recessive blood clotting disorder with an incidence of approximately one in two million, which is caused mainly by mutations in the F13A1 gene. Recently, we identified a Chinese family with FXIII deficiency carrying a likely pathogenic variant and explored its pathogenic mechanism. Aim The aim of this study was to investigate the pathogenic mechanism associated with the Ser414 mutation in the F13A1 gene. Methods We performed clinical diagnosis, phenotypic assessment, and genetic analysis of the proband and her family members. Results The FXIII antigen level of the proband was 1.3%, which was significantly lower than the normal reference range. A mutation was identified through targeted next‐generation sequencing (NGS). The effects of these variations on protein function were assessed using bioinformatics tools. Homology analysis revealed that Ser414 was also highly conserved in homologous species. Protein model analysis revealed that the Ser414Leu variation could induce alterations in the spatial structure of F13A1, potentially increasing its instability. This is the first time that F13A1 gene variants have been analyzed in a patient with FXIII deficiency, contributing to the expansion of the pathogenic variant database for congenital FXIII deficiency. Conclusion These findings provide valuable data accumulation that can contribute to the prevention of congenital FXIII deficiency, the exploration of potential pathogenic mechanisms, and the enrichment of genetic mutation databases.
Wang et al. (Thu,) studied this question.