Hereditary protein C deficiency: The Australian experience
- Author(s)
- Doig, RG; Begley, CG; McGrath, KM;
- Details
- Publication Year 1994,Volume 1,Issue #1,Page 49-54
- Journal Title
- CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS
- Publication Type
- Journal Article
- Abstract
- Hereditary protein C deficiency (HPCD) is a recognized risk factor for thrombotic disease. To examine the underlying genetic defect in more detail, the protein C gene was examined in eight families from Australia. All exons and intron/exon boundaries containing the translated sequence of the protein C gene were amplified using the polymerase chain reaction (PCR) and sequenced directly. All families were identified because of a thrombotic event in the proband. Six families had type I deficiency and two had type II. Seven mutations were found in eight different families (two apparently unrelated families shared the same mutation). Five of them were point mutations leading to amino acid substitutions, most of which occurred in the serine protease domain of the mature protein. One mutation produced a premature stop codon, and another led to a putative splice site mutation. All of these mutations could be detected using restriction enzyme digestion or single-strand conformation polymorphism (SSCP) analysis of PCR-derived DNA. These results confirm the genetic heterogeneity of HPCD. Genetic diagnosis is feasible in families in whom the defect in the proband has been identified; it overcomes some of the limitations of protein-based diagnostic methods.
- Publisher
- LIPPINCOTT-RAVEN PUBL
- Keywords
- NEONATAL PURPURA FULMINANS; ENDOPLASMIC-RETICULUM; POINT MUTATIONS; DUTCH FAMILIES; THROMBOSIS; BLOOD; ACTIVATION; TRANSPORT; SECRETION; COFACTOR
- Publisher's Version
- https://doi.org/10.1177/107602969500100108
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1994-01-01 12:00:00