A PHENOTYPICALLY NEUTRAL DIMORPHISM OF PROTEIN-S - THE SUBSTITUTION OF LYS155 BY GLU IN THE 2ND EGF DOMAIN PREDICTED BY AN A-BASE TO G-BASEEXCHANGE IN THE GENE

During the course of structural gene analysis of a family with type II I protein S deficiency, we found a novel DNA polymorphism: an A or G v ariation at nucleotide 732 in exon 6 of the PS-alpha gene. This A to G mutation would lead to a substitution of Lys155 by Glu in the second EGF domain. Linkage study with restriction enzyme analysis using mutag enic PCR strategy showed that the same mutation was also present in th ree other members of the patient's family and two individuals from an unrelated kindred, while they all had normal amounts of both immunolog ical and functional PS levels. Restriction enzyme analysis of 182 norm al Japanese genomic samples showed that 1.65% of normal population wer e heterozygotes for this variant allele. These findings suggest that t his substitution in exon 6 is not responsible for the type III protein S deficiency but a phenotypically neutral polymorphism. Hereby we des ignate this polymorphism as PS-732.