Thirty-three Novel Mutations in the Protein C Gene

Martine Alhenc-Gelas; Sophie Gandrille; Marie-Laurence Aubry; Martine Aiach; deficiencies and the French INSERM network on molecular abnormalities responsible for protein C and protein S

doi:10.1055/s-0037-1613762

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 83(01): 86-92
DOI: 10.1055/s-0037-1613762

Commentary

Schattauer GmbH

Thirty-three Novel Mutations in the Protein C Gene

Martine Alhenc-Gelas

¹From the Laboratoire d’Hémostase, Hôpital Broussais - AP-HP and Unité INSERM 428, Faculté de Pharmacie, Université René Descartes, Paris, France

,

Sophie Gandrille

¹From the Laboratoire d’Hémostase, Hôpital Broussais - AP-HP and Unité INSERM 428, Faculté de Pharmacie, Université René Descartes, Paris, France

,

Marie-Laurence Aubry

¹From the Laboratoire d’Hémostase, Hôpital Broussais - AP-HP and Unité INSERM 428, Faculté de Pharmacie, Université René Descartes, Paris, France

,

Martine Aiach

¹From the Laboratoire d’Hémostase, Hôpital Broussais - AP-HP and Unité INSERM 428, Faculté de Pharmacie, Université René Descartes, Paris, France

,

deficiencies and the French INSERM network on molecular abnormalities responsible for protein C and protein S

› Author Affiliations

Abstract

Summary

We analyzed the protein C gene (PROC) with the denaturing gradient gel electrophoresis (DGGE) scanning strategy in a series of 129 patients with suspected protein C (PC) deficiency (93 with low plasma PC levels and 36 with borderline level). At least one sequence variation was found in 104 of the 129 patients. Thirty-nine sequence variations (found in 72 patients) were already reported detrimental mutations. Thirty-three were novel sequence variations, of which 19 (found in 25 patients) were probably detrimental. Five novel mutations (A1T, R9H, S11R, S12R and K193Q) were associated with qualitative plasma PC deficiency, suggesting or confirming the functional importance of amino acids at these positions. This strategy confirmed the diagnosis of inherited PC deficiency in 79/93 (84.9%) patients with low plasma PC levels and 14/36 (38.8%) patients with borderline values. In order to explain abnormal PC levels observed in patients who did not carry detrimental mutations, screening for the -1654C/T and -1641A/G PROC promoter polymorphisms known to influence plasma PC concentrations was performed. The frequency of the CG allele associated with lower PC concentrations was slightly but not significantly lower in 82 heterozygotes for detrimental PROC gene mutations than in 36 patients with no identified detrimental mutations.

Keywords

Protein C - thrombosis - coagulation - gene

Full Text

References

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