TY - JOUR
T1 - Molecular bases of type II protein S deficiency
T2 - The I203-D204 deletion in the EGF4 domain alters GLA domain function
AU - Baroni, M.
AU - Mazzola, G.
AU - Kaabache, T.
AU - Borgel, D.
AU - Gandrille, S.
AU - Vigano' D'Angelo, S.
AU - Marchetti, G.
AU - Di Iasio, M. G.
AU - Pinotti, M.
AU - D'Angelo, A.
AU - Bernardi, F.
PY - 2006/1
Y1 - 2006/1
N2 - Objective: To characterize the first type II protein S (PS) deficiency affecting the epidermal growth factor (EGF)4 domain, a calcium-binding module with poorly defined functional role. Patients: The proband suffered from recurrent deep vein thrombosis and showed reduced PS anticoagulant activity (31%), and total, free PS antigen and C4bBP levels in the normal range. Results: Reverse transcription-polymerase chain reaction analysis showed the presence of the IVSg-2A/T splicing mutation that, by activating a cryptic splice site, causes the deletion of codons Ile203 and Asp204. Free PS, immunopurified from proband's plasma, showed an altered electrophoretic pattern in native condition or in the presence of Ca2+. The recombinant PS (rPS) mutant showed reduced nticoagulant (2+-dependent conformation-specific monoclonal antibodies for GLA domain was significantly reduced. Conclusions: These data aid in the characterization of the functional role of the EGF4 domain in the anticoagulant activities of PS and in defining the thrombophilic nature of type II PS deficiency.
AB - Objective: To characterize the first type II protein S (PS) deficiency affecting the epidermal growth factor (EGF)4 domain, a calcium-binding module with poorly defined functional role. Patients: The proband suffered from recurrent deep vein thrombosis and showed reduced PS anticoagulant activity (31%), and total, free PS antigen and C4bBP levels in the normal range. Results: Reverse transcription-polymerase chain reaction analysis showed the presence of the IVSg-2A/T splicing mutation that, by activating a cryptic splice site, causes the deletion of codons Ile203 and Asp204. Free PS, immunopurified from proband's plasma, showed an altered electrophoretic pattern in native condition or in the presence of Ca2+. The recombinant PS (rPS) mutant showed reduced nticoagulant (2+-dependent conformation-specific monoclonal antibodies for GLA domain was significantly reduced. Conclusions: These data aid in the characterization of the functional role of the EGF4 domain in the anticoagulant activities of PS and in defining the thrombophilic nature of type II PS deficiency.
KW - Activated protein C pathway
KW - Epidermal growth factor domain
KW - Protein S deficiency
KW - Recombinant protein S
KW - Venous thrombosis
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U2 - 10.1111/j.1538-7836.2005.01682.x
DO - 10.1111/j.1538-7836.2005.01682.x
M3 - Article
C2 - 16409468
AN - SCOPUS:33644855157
SN - 1538-7933
VL - 4
SP - 186
EP - 191
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 1
ER -