Thromb Haemost 1993; 70(04): 636-641
DOI: 10.1055/s-0038-1649641
Original Article
Coagulation
Schattauer GmbH Stuttgart

A Compound Heterozygous Protein C Deficiency with a Single Nucleotide G Deletion Encoding Gly-381 and an Amino Acid Substitution of Lys for Gla-26

Masaru Ido
The Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Tsu-City, Mie, Japan
,
Michiaki Ohiwa
The Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Tsu-City, Mie, Japan
,
Tatsuya Hayashi
The Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Tsu-City, Mie, Japan
,
Junji Nishioka
The Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Tsu-City, Mie, Japan
,
Tsuyoshi Hatada
The Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Tsu-City, Mie, Japan
,
Yasuyuki Watanabe
The Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Tsu-City, Mie, Japan
,
Hideo Wada
1   The Second Department of Internal Medicine, Mie University School of Medicine, Tsu-City, Mie, Japan
,
Shigeru Shirakawa
1   The Second Department of Internal Medicine, Mie University School of Medicine, Tsu-City, Mie, Japan
,
Koji Suzuki
The Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Tsu-City, Mie, Japan
› Author Affiliations
Further Information

Publication History

Received 15 January 1993

Accepted after revision 28 May 1993

Publication Date:
05 July 2018 (online)

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Summary

We report genetic abnormalities of protein C gene in a male infant who developed neonatal purpura fulminans. DNA-sequence analysis of all exons in protein C gene in this family revealed two mutations. The first abnormality, derived from the mother, was a deletion of one of four consecutive G at nucleotide number 10758 in exon IX which would result in a frame shift mutation and completely change amino acid sequence from Gly381 in the carboxyl-terminal region of protein C. The second abnormality, derived from the father, was a single nucleotide mutation from G to A in the codon (GAG to AAG) at nucleotide number 2977 in exon III, which would result in a substitution of Lys for γ-carboxyglutamic acid (Gla)26. This change would be responsible for the reduced immunological protein C levels of the patient and the father, estimated by a monoclonal antibody which recognizes the Gla-domain in a Ca2+-dependent manner (3.8% and 57%, respectively). Partially purified abnormal protein C from the father’s plasma showed a normal amidolytic activity and a change in the electrophoretic mobility. We detected the above mutations in his family members using two methods; one was a creation of new restriction enzyme sites using mutagenic primers and the other was single nucleotide primer extension. Both methods are rapid and useful for the diagnosis of prenatal protein C abnormalities.