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Thromb Haemost 1994; 72(06): 814-818
DOI: 10.1055/s-0038-1648967
Original Article
Schattauer GmbH Stuttgart

Compound Heterozygous Protein C Deficiency Caused by Two Mutations, Arg-178 to Gin and Cys-331 to Arg, Leading to Impaired Secretion of Mutant Protein C

Authors

  • Yuichi Sugahara

    The First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan

  • Osamu Miura

    The First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan

  • Shinsaku Hirosawa

    The First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan

  • Nobuo Aoki

    The First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Further Information

Publication History

Received 26 April 1994

Accepted after resubmission 19 August 1994

Publication Date:
06 July 2018 (online)

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Summary

The protein C gene in a patient apparently homozygous for protein C deficiency was analyzed. Two different point mutations, each located in a different allele, were detected to reveal that the patient is a compound heterozygote. Mutation of Arg-178 (CGG) to Gin (CAG) [mutation I] was detected in exon VII, in the vicinity of activation peptide cleavage site by thrombin. Mutation of Cys-331 (TGC) to Arg (CGC) [mutation II] was found in exon IX, at one of the sites involved in disulfide bond formation in the catalytic domain of the heavy chain. The alteration of Cys-331 to Arg disables the formation of the disulfide bond and would alter the protein conformation. Transient expression assays using COS-7 cells transfected with protein C expression vectors containing each one of these two mutations suggested that each of the two mutations would lead to the protein C deficiency by an impairment of secretion of the respective mutant proteins.