Summary
A 50-year-old Japanese man who had experienced recurrent episodes of venous thrombosis
was found to have a hereditary protein S deficiency. The amount of total protein S
antigen in plasma was reduced by approximately 50% in the patient and his two sons.
DNA sequence analysis revealed a novel nonsense mutation, TAG for Gin 522 (CAG), in
exon 14 of the protein S gene. Family studies performed by mutagenic PCR followed
by restriction enzyme digestion showed that the proband and his two sons were heterozygous
for this mutation. An mRNA-based analysis indicated that transcripts of the mutated
allele were markedly reduced in the platelets of the affected individuals. Immunoblot
analysis failed to detect the truncated mutant of protein S in the plasma or platelets
of affected members. Our results demonstrated that this novel nonsense mutation was
responsible for the quantitative deficiency of protein S.
