A Quantitative Protein S Deficiency Associated with a Novel Nonsense Mutation and Markedly Reduced Levels of Mutated mRNA

Tomio Yamazaki; Motohiro Hamaguchi; Akira Katsumi; Kazuo Kagami; Tetsuhito Kojima; Junki Takamatsu; Hidehiko Saito

doi:10.1055/s-0038-1649780

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1995; 74(02): 590-595
DOI: 10.1055/s-0038-1649780

Original Article

Clinical Studies

Schattauer GmbH Stuttgart

A Quantitative Protein S Deficiency Associated with a Novel Nonsense Mutation and Markedly Reduced Levels of Mutated mRNA

Authors

Tomio Yamazaki

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Motohiro Hamaguchi

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Akira Katsumi

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Kazuo Kagami

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Tetsuhito Kojima

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Junki Takamatsu

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Hidehiko Saito

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

Abstract

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Summary

A 50-year-old Japanese man who had experienced recurrent episodes of venous thrombosis was found to have a hereditary protein S deficiency. The amount of total protein S antigen in plasma was reduced by approximately 50% in the patient and his two sons. DNA sequence analysis revealed a novel nonsense mutation, TAG for Gin 522 (CAG), in exon 14 of the protein S gene. Family studies performed by mutagenic PCR followed by restriction enzyme digestion showed that the proband and his two sons were heterozygous for this mutation. An mRNA-based analysis indicated that transcripts of the mutated allele were markedly reduced in the platelets of the affected individuals. Immunoblot analysis failed to detect the truncated mutant of protein S in the plasma or platelets of affected members. Our results demonstrated that this novel nonsense mutation was responsible for the quantitative deficiency of protein S.

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Referenzen

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