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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

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
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Publikationsverlauf

Received 10. Januar 1995

Accepted after revision 20. März 1995

Publikationsdatum:
04. Juli 2018 (online)

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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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