A 76-year-old Japanese woman was hospitalized for ileus symptoms caused by extensive thrombosis of the superior mesen-teric vein. Because laboratory test results suggested type III protein S (PS) deficiency, molecular changes in PS were investi-gated.A single-base transition, CCG to CTG at codon 626 in exon XV, resulting in the missense mutation Pro626Leu, was identified in an allele of the patient and in her son. Reverse transcriptase polymerase chain reaction analysis indicated the presence of both normal and mutant types of PS messages in platelet-derived messenger RNAs. Our findings thus suggest that Pro626 in SHBG-like domain 7 may be crucial for in vivo antithrombotic activity of the PS molecule.
Protein S deficiency SHBG-like domain Missense mutation Superior mesenteric venous thrombosis Pro626Leu
This is a preview of subscription content, log in to check access.
van Wijinen M, Stam JG, van’t Veer C, et al. The interaction of protein S with the phospholipid surface is essential for the activated protein C-independent activity of protein S.Thromb Haemost. 1996;76:397–403.CrossRefGoogle Scholar
Dahlbäck B. Interaction between complement component C4b- binding protein and vitamin K-dependent protein S. A link between blood coagulation and the complement system.Scand J Clin Lab Inves. 1985;177(suppl):33–41.Google Scholar
Simmonds RE, Ireland H, Lane DA, et al. Clarification of the risk for venous thrombosis associated with hereditary protein S deficiency by investigation of a large kindred with a characterized gene defect.Ann Intern Med. 1998;128:8–14.CrossRefPubMedPubMedCentralGoogle Scholar
Hayashi T, Nishioka J, Shigekiyo T, Saito S, Suzuki K. Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys- 155 in the second epidermal growth factor-like domain of Protein S.Blood. 1994;83:683–690.PubMedGoogle Scholar
Yamazaki T, Katsumi A, Okamoto Y, et al. Two distinct novel splice site mutations in a compound heterozygous patients with protein S deficiency.Thromb Haemost. 1997;77:14–20.PubMedPubMedCentralCrossRefGoogle Scholar
Diepstraten CM, Ploos van Amstel JK, Reitsma PH, Bertina RM. A CCA/CCG neutral polymorphism in the codon for Pro 626 in the human protein S alpha (PROS1).Nuclei Acids Res. 1991;19:5091.CrossRefGoogle Scholar
Nyberg P, Dahlbäck B, Garcia de Frutos P. The SHBG-like region of protein S is crucial for factor V-dependent APC cofactor function.FEBS Lett. 1998;433:28–32.CrossRefPubMedGoogle Scholar
Gandrille S, Borgel D, Ireland H, et al. Protein S Deficiency: a data- base of mutations.Thrombo Haemast. 1997;77:1201–1214.CrossRefGoogle Scholar
Espinosa-Parrilla Y, Yamazaki T, Sala N, Dahlbäck B, Garcia de Frutos P. Protein S secretion differences of missense mutation account for phenotypic heterogeneity.Blood. 2000;95:173–179.PubMedGoogle Scholar
Gandrille S, Borgel D, Sala N, et al. Protein S deficiency: a database of mutations-summary of the first update.Thrombo Haemast. 2000;84:918.CrossRefGoogle Scholar
Zoller B, Garcia de Frutos P, Dahlbäck B. Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of same genetic disease.Blood. 1995;85:3524–3531.PubMedGoogle Scholar
Chen MC, Brown MC, Willson RA, Nicholls S, Surawicz CM. Mesenteric vein thrombosis. Four cases and review of the literature.Dig Dis. 1996;14:382–389.CrossRefPubMedGoogle Scholar