Co-segregation of the PROS1 locus and protein S deficiency in families having no detectable mutations in PROS1.
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.
Lanke
E
E
Department for Coagulation Disorders, University Hospital, Malmö, Sweden.
Johansson
A M
AM
Hillarp
A
A
Lethagen
S
S
Zöller
B
B
Dahlbäck
B
B
Halldén
C
C
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*
D017293:Protein S