Partial protein S gene deletion in a family with hereditary thrombophilia
HK Ploos van Amstel, MV Huisman, PH Reitsma, J Wouter ten Cate and RM Bertina
Department of Hematology, Leiden University Hospital, The Netherlands.
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.
Volume 73,
Issue 2,
pp. 479-483,
02/01/1989
Copyright © 1989 by The American Society of Hematology
