Hum. Reprod. Advance Access originally published online on November 11, 2006
Human Reproduction 2007 22(3):864-868; doi:10.1093/humrep/del436
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Variations in the thrombomodulin and endothelial protein C receptor genes in couples with recurrent miscarriage
1 Folkhälsan Institute of Genetics, University of Helsinki 2 Department of Obstetrics and Gynecology and 3 Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland
4 To whom correspondence should be addressed at: Department of Clinical Genetics, Helsinki University Hospital, POB 140, FIN-00029 HUS, Helsinki, Finland. E-mail: kristiina.aittomaki{at}hus.fi
BACKGROUND: Recurrent miscarriage (RM) has been suggested to be caused by mutations in genes coding for various coagulation factors resulting in thrombophilia. Mouse models indicate that genes involved in the protein C anticoagulant pathway are essential for normal embryonic development. Loss of function of two of these genes, thrombomodulin (TM) and endothelial protein C receptor (EPCR), causes embryonic lethality in mice. The aim of this study was to determine whether variations in the human TM or EPCR genes are associated with an increased risk for RM. METHODS: Forty-six RM patients and 191 controls were screened for mutations in TM and EPCR using denaturing high-performance liquid chromatography (DHPLC). The partners of 40 RM patients were also screened. RESULTS: One exonic and one intronic variation in TM and two exonic and two intronic sequences in EPCR were detected. Four variants were common in both patients and controls. A previously identified truncating mutation in EPCR, suggested to have a role in pregnancy complications, was identified in two patients and one control. A novel deletion in the 3'UTR region of TM was detected, but its significance remains unsolved. CONCLUSIONS: These data suggest that mutations in the TM or EPCR genes are not a major cause of RM, although they may exert a modifier effect in combination with other variants.
Key words: DHPLC/endothelial protein C receptor/miscarriage/recurrent spontaneous abortion/thrombomodulin
Submitted on July 14, 2006; resubmitted on September 14, 2006; accepted on October 16, 2006.
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