Severe homozygous protein C deficiency: identification of a splice site missense mutation (184, Q-->H) in exon 7 of the protein C gene.
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 mutations, 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.
Molecular Genetics Department, Hospital Duran i Reynals, Barcelona, Spain.
J M
JM
Soria
D
D
Brito
J
J
Barceló
J
J
Fontcuberta
L
L
Botero
J
J
Maldonado
X
X
Estivill
N
N
Sala
D001483:Base Sequence; D001780:Blood Coagulation Tests; D004274:DNA, Recombinant; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D011695:IgA Vasculitis / Q000235:genetics*; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation; D011486:Protein C / Q000235:genetics; D020151:Protein C Deficiency
D004274:DNA, Recombinant; D011486:Protein C