Analysis three abnormal Protein S genes in a patient with pulmonary embolism

A protein S (PS) abnormality is a hereditary risk factor for thromboembolism. A 33-year-old female had a left deep vein thrombosis (DVT) and mild pulmonary embolism (PE). Her PS antigen level was 34.7% and the activity level was less than 10%. Genetic analysis identified three missense mutations in PS: the D38Y mutation in exon 3, and the T589I mutation and P626L mutations in exon 15. The D38Y mutation has not been reported previously. An analysis of the patient's family revealed that all members of the family had some PS gene mutation. The D38Y and T589I mutations were both in same allele, the P626L mutation was in another allele. The expression of PS mutations in COS-7 cells revealed that PS activity and antigen were markedly decreased in the D38Y mutation but not in the T589I mutation. The expression of the P626L mutation in baby hamster kidney (BHK) cells showed the PS activity and antigen to be markedly decreased in comparison to the wild type.