Poor Relationship between Phenotypes of Protein S Deficiency and Mutations in the Protein S Alpha Gene

José Hermida; Elena M. Faioni; Pier Mannuccio Mannucci

doi:10.1055/s-0037-1614891

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(06): 1634-1638
DOI: 10.1055/s-0037-1614891

Rapid Communication

Schattauer GmbH

Poor Relationship between Phenotypes of Protein S Deficiency and Mutations in the Protein S Alpha Gene

Authors

José Hermida

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, I.R.C.C.S. Maggiore Hospital and Department of Internal Medicine, University of Milano, Milano, Italy
Elena M. Faioni

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, I.R.C.C.S. Maggiore Hospital and Department of Internal Medicine, University of Milano, Milano, Italy
Pier Mannuccio Mannucci

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, I.R.C.C.S. Maggiore Hospital and Department of Internal Medicine, University of Milano, Milano, Italy

Abstract

Summary

By single strand conformational polymorphism, nucleotide sequencing and enzyme restriction, we analyzed the protein S α gene in 17 protein S-deficient probands and in their available family members. The relationship between genotype and phenotype was also evaluated. Twelve different sequence variations were identified in 17 probands. Ten were putative causal mutations distributed in 16 probands: 4 were nonsense, 5 missense and one a splice site mutation. In most families in which a mutation was identified, more than one phenotype of PS deficiency was present. The same splice site mutation (intron j G-A, exon 10+5) was associated with type I deficiency in one family and with type I/III in another unrelated family. A phenotypic discrepancy was also observed for the Arg474Pro, Gly597Asp and Arg410stop mutations. Glu26Ala, previously reported in kindreds with type I deficiencies, was found in association with I, II and III phenotypes in four unrelated kindreds. Phenotypic analysis of protein S deficiency is poorly related to the underlying genetic defect.

Key Words

Protein S α gene - mutations - phenotype - protein S Heerlen

Full Text

References

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