Three Missense Mutations in the Protein C Heavy Chain Causing Type I and Type II Protein C Deficiency

Toshiyuki Miyata; Yan-Zhen Zheng; Toshiyuki Sakata; Nobuko Tsushima; Hisao Kato

doi:10.1055/s-0038-1642381

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1994; 71(01): 032-037
DOI: 10.1055/s-0038-1642381

Review Article

Schattauer GmbH Stuttgart

Three Missense Mutations in the Protein C Heavy Chain Causing Type I and Type II Protein C Deficiency

Toshiyuki Miyata

¹The Laboratory of Thrombosis Research and Division of Etiology and Pathogenesis, National Cardiovascular Center Research Institute, Fujishirodai 5, Suita 565, Japan

,

Yan-Zhen Zheng

¹The Laboratory of Thrombosis Research and Division of Etiology and Pathogenesis, National Cardiovascular Center Research Institute, Fujishirodai 5, Suita 565, Japan

,

Toshiyuki Sakata

²Department of Clinical Laboratory, National Cardiovascular Center, Fujishirodai 5, Suita 565, Japan

,

Nobuko Tsushima

³Department of Medicine, National Cardiovascular Center, Fujishirodai 5, Suita 565, Japan

,

Hisao Kato

¹The Laboratory of Thrombosis Research and Division of Etiology and Pathogenesis, National Cardiovascular Center Research Institute, Fujishirodai 5, Suita 565, Japan

› Institutsangaben

Abstract

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Summary

We have studied the molecular basis of protein C deficiency in three families with a history of thromboembolic disease. An approximately 50% reduction in both functional and immunologic levels of protein C was detected in the plasma from two unrelated patients, designated protein C Osaka 1 and protein C Osaka 2. An approximately 50% reduction in functional level but normal immunologic level of protein C was detected in plasma from a third patient, designated protein C Osaka 3. DNA sequencing of the amplified DNA revealed one missense mutation in each case. Additional mutations in the coding sequence were excluded by DNA sequencing of all protein C exons. We identified a C-to-T change at nucleotide number 6,218 of the protein C gene in protein C Osaka 1. This results in the amino acid substitution of Arg-169 by Trp at the a-thrombin cleavage site. In protein C Osaka 2, a G-to-A change at nucleotide number 8,807 was identified leading to the amino acid substitution of Met-364 by lie in the protease domain. This substitution may impair the synthesis or stability of protein C Osaka 2. In protein C Osaka 3, a G-to-C change at nucleotide number 8,868 was identified. This results in substitution of Gly-385 by Arg in the protease domain. Based on these, it was concluded that Arg-169-to-Trp mutation and Met-364-to-Ile mutation cause type I protein C deficiency and Gly-385-to-Arg mutation causes type II deficiency.

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Referenzen

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