ANALYSIS FOR HETEROZYGOSITY OF PROTEIN-S MESSENGER-RNA - APPLICATION TO GENETIC SCREENING AND FAMILY STUDIES IN HEREDITARY PROTEIN-S DEFICIENCY

We genetically screened patients with hereditary protein S deficiency for heterozygosity of protein S mRNA using PCR-RFLP for Pro626 polymor phism. All patients who showed hemizygous state of protein S mRNA, cha racterized by markedly decreased levels of one allele, had a phenotype of type I protein S deficiency. A putative mutation, such as a nonsen se or splice site mutation, in the silent alleles may have affected th e mutated mRNA metabolism and reduced the mutated mRNA accumulation, a nd consequently resulted in type I protein S deficiency in these patie nts, We also applied this mRNA-based analysis to family studies in her editary protein S deficiency, In a family with type I protein S defici ency, all affected individuals showed a loss of one allele at the mRNA level and the silent allele cosegregated with the disease phenotype. Detection of hemizygous expression of protein S mRNA provided direct e vidence for type I protein S deficiency without further precise geneti c analysis. Our findings indicate that this mRNA-based analysis can be a useful strategy for genetic screening and family studies in heredit ary protein S deficiency.