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A NEW MUTATION WITHIN PROTEIN Z GENE IS ASSOCIATED WITH VERY LOW PROTEIN LEVELS IN WOMEN WITH FETAL LOSS
Abstract number: P-S-100
Grandone1 E., Colaizzo1 D., Cappucci1 F., D'Ambrosio1 R., Vecchione1 G., Margaglione2 M.
11Atherosclerosis and Thrombosis, IRCCS Casa Sollievo della Sofferenza, S.Giovanni Rotondo 22Medical Genetics, University of Foggia, Foggia, Italy
How-to-cite Grandone E, Colaizzo D, Cappucci F, D'Ambrosio R, Vecchione G, Margaglione M. A NEW MUTATION WITHIN PROTEIN Z GENE IS ASSOCIATED WITH VERY LOW PROTEIN LEVELS IN WOMEN WITH FETAL LOSS. J Thromb Haemost 2007; 5 Supplement 2: P-S-100
Abstract
Introduction: Protein Z (PZ) is a vitamin K-dependent glycoprotein regulating coagulation cascade because of protein Z-dependent protease inhibitor. Reduced circulating levels of PZ have been suggested to play a role in the occurrence of bleeding and deep vein thrombosis) and in early, as well as late fetal losses, although data about this issue are conflicting.
Methods: PZ levels were measured in 124 women with unexplained fetal losses and compared with those of 104 parous controls.
Direct sequencing of the PZ gene was carried out. Intron C G-42A gene variant was also investigated.
Results: Seven out 124 (5.6%) cases and 5 out 104 (4.8%) controls showed PZ levels under the 5th percentile (0.52 ?g/ml). Intron C G-42A gene variant was also investigated and found in 5 (71.4%,) cases and 21 [20.2%, Fisher Exact test p= 0.008; OR: 9.88 (95%CI: 2.03-47.1)] controls. In addition, 2 patients with PZ levels under the 2.5 percentile carried a new missense mutation within the exon 8 causing the substitution of a hydrophobic residue (Leu) with a hydrophilic one (Arg) in the trypsin-like serine protease domain.
Conclusions: Intron C G-42A gene variant is significantly associated with the occurrence of fetal losses.
A new missense mutation within the exon 8 (T15021G, accession number AF 440358) causing the substitution of a hydrophobic residue (Leu) with a hydrophilic one (Arg) in the trypsin-like serine protease domain of the protein was found in two patients.
This residue is highly conserved among different species. This new sporadic mutation within the PZ gene could explain the very low PZ levels in our patients.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
01/08/2007
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| Time: |
00:00-00:00
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| Session name: |
XXIst ISTH Congress |
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| Location: |
Oxford, UK |
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