Summary
We report the genetic abnormalities in the protein C genes of a Spanish child with
neonatal purpura fulminans and disseminated intravascular coagulation, associated
with undetectable protein C levels. Direct sequencing of the nine protein C gene exons
and their splice junctions indicated that the proband is a compound heterozygote with
two mutant protein C gene alleles, Y124C and Q132X, that do not express protein C
in plasma. The Y124C mutation was inherited from the mother and is due to a novel
A to G transition at nucleotide 3416, which results in the substitution of cysteine
for tyrosine 124, a highly conserved amino acid in EGF-like domains. The paternal
inherited mutation (Q132X) is a C to T transition at nucleotide 3439, which replaces
glutamine 132 with a Stop codon signal. This mutation, if expressed, should result
in the synthesis of a truncated protein of 131 amino acids. Y124C or Q132X are present
in the heterozygous state in the asymptomatic parents and siblings of the proband,
all of which have half the normal plasma levels of protein C. Q123X has also been
identified in families where type I PC deficiency is inherited as a clinically dominant
trait. Therefore, the presence of the same mutation in a family showing a clinically
recessive pattern of inheritance indicates that other factors, apart from the type
of protein C gene mutation, are responsible for the clinical expression of protein
C deficiency.
