Simmonds, RE; Ireland, H; Kunz, G; Lane, DA; Bhavnani, M; Castaman, G; ... Walker, ID; + view all Simmonds, RE; Ireland, H; Kunz, G; Lane, DA; Bhavnani, M; Castaman, G; Hambley, H; Laffan, M; OConnor, N; Sas, G; Tew, CJ; Walker, ID; - view fewer (1996) Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis. BLOOD , 88 (11) 4195 - 4204.
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Protein S is a protein C-dependent and independent inhibitor of the coagulation cascade. Deficiency of protein S is an established risk factor for venous thromboembolism. We have used a strategy of specific amplification of the coding regions and intron/exon boundaries of the active protein S gene (PROS1) and direct single-strand solid phase sequencing, to seek mutations in 35 individuals with phenotypic protein S deficiency. Nineteen point mutations (16 novel) in 19 probands (or relatives of probands) with venous thromboembolism are reported here. Fifteen of the 19 mutations were expected to be causal and included 10 missense mutations (Lys9Glu, Glu26Ala, Gly54Glu, Cys145Tyr. Cys200Ser, Ser283Pro, Gly340Asp. Cys408Ser, Ser460Pro, and Cys625Arg). Three of the 15 mutations resulted in premature stop codons (delete T 635 producing a stop codon at position 126, Lys368stop and Tyr595stop) and two were at intron/exon boundaries (+1 G to A in intron d and +3 A to C in intron j). Of the remaining four mutations, three were within intronic sequence and one was a silent mutation within the coding region and did not alter amino acid composition. In two of the 10 missense mutations, reduced plasma protein S activity compared with antigen level suggested the presence of variant (type II) protein S. (C) 1996 by The American Society of Hematology.
|Title:||Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis|
|Keywords:||ANDROGEN-BINDING PROTEIN, C4B-BINDING PROTEIN, VENOUS THROMBOSIS, POINT MUTATIONS, NEUTRAL DIMORPHISM, BLOOD-COAGULATION, FUNCTIONAL ASSAY, ALPHA PROS1, PS-ALPHA, CDNA|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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