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Thromb Haemost 1997; 77(01): 014-020
DOI: 10.1055/s-0038-1655729
Clinical Studies
Schattauer GmbH Stuttgart

Two Distinct Novel Splice Site Mutations in a Compound Heterozygous Patient with Protein S Deficiency

Tomio Yamazaki
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
,
Akira Katsumi
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
,
Yoshihiro Okamoto
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
2   The Department of Clinical Pharmacy, Faculty of Pharmacy, Meijo University, Nagoya
,
Toshio Takafuta
3   The Department of Hematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
,
Shinobu Tsuzuki
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
,
Kazuo Kagami
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
,
Isamu Sugiura
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
,
Tetsuhito Kojima
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
,
Kingo Fujimura
3   The Department of Hematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
,
Hidehiko Saito
1   The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
› Author Affiliations
Further Information

Publication History

Received 14 June 1996

Accepted after resubmisssion 08 October 1996

Publication Date:
11 July 2018 (online)

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Summary

Genetic analysis revealed two distinct novel splice site mutations in a compound heterozygous patient with protein S deficiency. The paternal mutation was a G-to-T transition at position -1 of the acceptor splice site of intron N (Mutation I), and the maternal mutation was a G-to-C transversion at position -1 of the donor splice site of intron C (Mutation II). Both splice site mutations decreased the mutated mRNA accumulation to the same extent, approximately 40% of the normal mRNA. However, the mutations were associated with different phenotypical expressions: the paternal mutant protein S was not detected in vivo, while the maternal mutant protein S was present in the plasma in reduced quantity. Because Mutation I caused a cryptic splicing in the mutated mRNA, resulting in a reading frameshift and premature termination, the predicted mutant protein S might be highly unstable. In contrast, Mutation II led to the substitution of Val46 by Leu, which might be much less deleterious for the synthesis, secretion and stability of the predicted mutant protein S. It was supposed that the different post-translational metabolisms produced the distinct phenotypical expressions of the mutations.

 

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