Molecular bases of type II protein S deficiency: The I203-D204 deletion in the EGF4 domain alters GLA domain function

M. Baroni, G. Mazzola, T. Kaabache, D. Borgel, S. Gandrille, S. Vigano' D'Angelo, G. Marchetti, M. G. Di Iasio, M. Pinotti, A. D'Angelo, F. Bernardi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)186-191
Number of pages6
JournalJournal of Thrombosis and Haemostasis
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 2006

Fingerprint

Protein S Deficiency
Protein S
Anticoagulants
RNA Splice Sites
Recombinant Proteins
Epidermal Growth Factor
Codon
Venous Thrombosis
Reverse Transcription
Reference Values
Monoclonal Antibodies
Calcium
Antigens
Polymerase Chain Reaction
Mutation

Keywords

  • Activated protein C pathway
  • Epidermal growth factor domain
  • Protein S deficiency
  • Recombinant protein S
  • Venous thrombosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Molecular bases of type II protein S deficiency : The I203-D204 deletion in the EGF4 domain alters GLA domain function. / Baroni, M.; Mazzola, G.; Kaabache, T.; Borgel, D.; Gandrille, S.; Vigano' D'Angelo, S.; Marchetti, G.; Di Iasio, M. G.; Pinotti, M.; D'Angelo, A.; Bernardi, F.

In: Journal of Thrombosis and Haemostasis, Vol. 4, No. 1, 01.2006, p. 186-191.

Research output: Contribution to journalArticle

Baroni, M, Mazzola, G, Kaabache, T, Borgel, D, Gandrille, S, Vigano' D'Angelo, S, Marchetti, G, Di Iasio, MG, Pinotti, M, D'Angelo, A & Bernardi, F 2006, 'Molecular bases of type II protein S deficiency: The I203-D204 deletion in the EGF4 domain alters GLA domain function', Journal of Thrombosis and Haemostasis, vol. 4, no. 1, pp. 186-191. https://doi.org/10.1111/j.1538-7836.2005.01682.x
Baroni, M. ; Mazzola, G. ; Kaabache, T. ; Borgel, D. ; Gandrille, S. ; Vigano' D'Angelo, S. ; Marchetti, G. ; Di Iasio, M. G. ; Pinotti, M. ; D'Angelo, A. ; Bernardi, F. / Molecular bases of type II protein S deficiency : The I203-D204 deletion in the EGF4 domain alters GLA domain function. In: Journal of Thrombosis and Haemostasis. 2006 ; Vol. 4, No. 1. pp. 186-191.
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