Partial protein S gene deletion in a family with hereditary thrombophilia.
Familial thrombophilia, the hereditary predisposition to venous thromboembolic disease, is associated with a protein S deficiency in approximately 8% of the cases. Laboratory measurements of total protein S antigen in affected families have indicated that heterozygotes, ie, individuals carrying both a normal and a defective protein S gene, are severely at risk of developing venous thrombosis at a young age. The recent isolation of protein S cDNA has enabled us to start a search for genetic defects in the protein S gene of heterozygotes. Using Southern blotting on probands of six unrelated families with hereditary protein S deficiency, one proband was found to have a grossly abnormal gene pattern. The abnormality appears to involve at least the deletion of the middle portion of the protein S coding sequence. Family analysis showed that the defect cosegregates with the protein S deficiency. These data agree with the notion that hereditary thrombophilia associated with protein S deficiency is indeed directly the result of a defect in the protein S gene.
Ploos van Amstel
H K
HK
Department of Hematology, Leiden University Hospital, The Netherlands.
Huisman
M V
MV
Reitsma
P H
PH
Wouter ten Cate
J
J
Bertina
R M
RM
D004252:DNA Mutational Analysis; D015342:DNA Probes; D006023:Glycoproteins / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D017293:Protein S; D013927:Thrombosis / Q000235:genetics*
D015342:DNA Probes; D006023:Glycoproteins; D017293:Protein S