Compound heterozygosity for one novel and one recurrent mutation in a Thaipatient with severe protein S deficiency

Homozygous or compound heterozygous protein S (PS) deficiency is a very rar e disorder in the anticoagulant system, that can lead to life-threatening t hrombotic complications shortly after birth. This report describes the resu lts of the genetic analysis of the PROS1 genes in a Thai girl patient. She was reported in 1990 as the first case with homozygous PS deficiency and ne onatal purpura fulminans. In the present report, we identified the mutation s in this patient by direct sequencing of PCR products representing all 15 exons of the PROS1 gene and their flanking intronic regions. The patient tu rned out to be compound heterozygous for two null mutations. One allele con tained a novel sequence variation, an A-insertion in an A(5)-tract covering codon 146 and 147, that results in a frameshift and a stop codon (TAA) at position 155. The other allele contained a nonsense mutation in exon 12 by a transition at codon 410 CGA (Arg) to TGA (stop). Cosegregation of PS defi ciency with these two genetic defects was observed in her family.