Protein S Deficiency with Two Novel PROS1 Gene Variants

Background and Aims: Protein S (PS) is a vitamin K-dependent glycoprotein synthesized by endothelial and somatic cells that acts as an anticoagulant in its free form and an inhibitor of the complement system in its bound form. Deficiency of PS is a congenital thrombophilia that can have significant clinical consequences. This study aimed to report the clinical and genetic characterization of four Iranian patients with PS deficiency. Materials and Methods: In this study, we investigated the genetic basis of PS deficiency in four Iranian patients from three unrelated families, including two females and two males with a mean age of 32.5(± 25.73) years. Whole blood was collected to measure PS total antigen levels and isolated genomic DNA, which was then amplified using polymerase chain reaction to direct sequencing of the PROS1 gene with the Sanger method. Each novel variation was subjected to in silico analysis. Results: Two novel variants in the PROS1 gene were identified: c.-196 C > G in exon 1 and c.198A > C in exon 2. In this setting, both variants were present in a heterozygous state in patient C1 and a homozygous state in patient C2. In addition, a silico analysis was conducted to assess the impact of the identified variants, showing that the c.198A > C variant was likely detrimental and the c.198A > C variant was likely pathogenic. Conclusion: The results highlight the heterogeneity of PS deficiency and the need for further investigation to identify additional mutations and understand the genetic basis of this condition in the Iranian population.