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.
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 humanTM 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.
Authors: Kristiina Rull; Liina Nagirnaja; Veli-Matti Ulander; Piret Kelgo; Tõnu Margus; Milja Kaare; Kristiina Aittomäki; Maris Laan Journal: J Clin Endocrinol Metab Date: 2008-09-09 Impact factor: 5.958
Authors: Mieke Delvaeye; Marina Noris; Astrid De Vriese; Charles T Esmon; Naomi L Esmon; Gary Ferrell; Jurgen Del-Favero; Stephane Plaisance; Bart Claes; Diether Lambrechts; Carla Zoja; Giuseppe Remuzzi; Edward M Conway Journal: N Engl J Med Date: 2009-07-23 Impact factor: 91.245
Authors: Paula Quintero-Ronderos; Eric Mercier; Jean-Christophe Gris; Clara Esteban-Perez; Harold Moreno-Ortiz; Dora Janeth Fonseca; Elkin Lucena; Daniel Vaiman; Paul Laissue Journal: Reprod Biol Endocrinol Date: 2017-12-01 Impact factor: 5.211