title: Co-segregation of the PROS1 locus and protein S deficiency in families having no detectable mutations in PROS1.
abstract: Inherited deficiency of protein S constitutes an important risk factor of venous thrombosis. Many reports have demonstrated that causative mutations in the protein S gene are found only in approximately 50% of the cases with protein S deficiency. It is uncertain whether the protein S gene is causative in all cases of protein S deficiency or if other genes are involved in cases where no mutation is identified. The aim of the current study was to determine whether haplotypes of the protein S gene cosegregate with the disease phenotype in cases where no mutations have been found. Eight protein S-deficient families comprising 115 individuals where previous DNA sequencing had failed to detect any causative mutations were analyzed using four microsatellite markers in the protein S gene region. Co-segregation between microsatellite haplotypes and protein S deficiency was found in seven of the investigated families, one family being uninformative. This suggests that the causative genetic defects are located in or close to the protein S gene in a majority of such cases where no mutations have been found.
authors.affiliation: Department for Coagulation Disorders, University Hospital, Malmö, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Lanke
authors.forename: A M
authors.initials: AM
authors.lastname: Johansson
authors.forename: A
authors.initials: A
authors.lastname: Hillarp
authors.forename: S
authors.initials: S
authors.lastname: Lethagen
authors.forename: B
authors.initials: B
authors.lastname: Zöller
authors.forename: B
authors.initials: B
authors.lastname: Dahlbäck
authors.forename: C
authors.initials: C
authors.lastname: Halldén
mesh_terms: D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006801:Humans; D040582:Inheritance Patterns; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D017293:Protein S / Q000235:genetics*; D018455:Protein S Deficiency / Q000235:genetics*
chemical_list: D017293:Protein S