Summary
Single strand conformation polymorphism (SSCP) analysis of exon 7 of the protein C
gene has identified a novel splice site missense mutation (184, Q → H), in a newborn
child with purpura fulminans and undetectable protein C levels. The mutation, seen
in the homozygous state in the child and in the heterozygous state in her mother,
was characterized and found to be a G to C nucleotide substitution at the -1 position
of the donor splice site of intron 7 of the protein C gene, which changes histidine
184 for glutamine (184, Q → H). According to analysis of the normal and mutated sequences,
this mutation should also abolish the function of the donor splice site of intron
7 of the protein C gene. Since such a mutation is compatible with the absence of gene
product in plasma and since DNA sequencing of all protein C gene exons in this patient
did not reveal any other mutation, we postulate that mutation 184, Q → H results in
the absence of protein C gene product in plasma, which could be the cause of the severe
phenotype observed in this patient.
