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.
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 gamma-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 Ca(2+)-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.
Ido
M
M
Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Japan.
Ohiwa
M
M
Hayashi
T
T
Nishioka
J
J
Hatada
T
T
Watanabe
Y
Y
Wada
H
H
Shirakawa
S
S
Suzuki
K
K
D015055:1-Carboxyglutamic Acid / Q000235:genetics*; D000941:Antigens / Q000097:blood; D001483:Base Sequence; D005091:Exons; D005220:Fathers; D005815:Genetic Code; D005998:Glycine / Q000235:genetics*; D006147:Guanine / Q000737:chemistry*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008239:Lysine / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency; D012016:Reference Values
D000941:Antigens; D011486:Protein C; D015055:1-Carboxyglutamic Acid; D006147:Guanine; D008239:Lysine; D005998:Glycine