A Rare Splicing Mutation in the PROS1 Gene of a Korean Patient with Type I Hereditary Protein S Deficiency

Abstract. Hereditary protein S (PS) deficiency (Gene ID: 5627; MIM # 176880) is a notable risk factor for recurrent venous thrombosis, inherited as an autosomal-dominant trait, either homozygous or hetero-zygous. It may be caused by point mutations in the gene (PROS1) encoding PS, which contains 15 exons on the chromosome 3q11.2. Only a few point mutations associated with the PROS1 gene in patients with hereditary PS deficiency have been reported. A 60-year-old woman was admitted for deep vein thrombosis (DVT) of the right lower extremity. Upon coagulation examination, both the free PS antigen level and the total PS antigen level were decreased, so the DNA-PCR products of all 15 exons, including the exon-intron boundaries of the PROS1, gene were directly sequenced. A substitution from guanine to adenine at position +5 of the donor splice site of intron 10 (c.1155+5G>A) was identified. Further familial study was performed, and the patient’s older sister was revealed to have the same mutation; she was already taking warfarin due to diagnosed pulmonary thromboembolism. Here we report a G to A transition at position +5 of intron 10 from the splice donor site as a rare case of a patient with type I hereditary PS deficiency i