Prevalence of JAK2V617F mutation in women with unexplained recurrent miscarriage

Abstract

To cite this article: Kaandorp SP, Lauw MN, van der Schoot CE, Goddijn M, van der Veen F, Koene HR, Biemond BJ, Middeldorp S. Prevalence of JAK2V617F mutation in women with unexplained recurrent miscarriage. J Thromb Haemost 2010; 8: 2837-9.The incidence of recurrent miscarriage (RM) amongst couples trying to conceive varies between 1% and 5% [1]. In 50-60% of couples the RM remains unexplained, even after thorough diagnostic evaluation. Therefore, the search for etiologic factors is very important for the couples and clinician alike.Polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) belong to the group of Philadelphia-chromosome negative myeloproliferative disorders (MPD). Pregnant women with MPD have an increased risk of pregnancy complications. Women with ET have a 3.4-fold (OR, 3.4; 95% CI, 3.0-3.9) increased risk of experiencing pregnancy loss (first trimester miscarriage, second trimester miscarriage and stillbirth) as compared with the general population [2]. Although the pathogenesis of the increased pregnancy loss is unclear, thrombotic complications, frequently observed in patients with PV and ET, are likely to play a role [3].Recently, a somatic gain-of-function mutation associated with the group of MPD was found in exon 14 of the JAK2 gene [4]. The JAK2V617F mutation is found in virtually all patients with PV and in half of patients with ET and IMF.In a large case-control study of 3496 women with pregnancy loss in the first pregnancy (first trimester miscarriage, second trimester miscarriage and stillbirth) the prevalence of the JAK2V617F mutation was significantly higher in cases than in controls with a single uncomplicated pregnancy (1.1% vs. 0.2%; OR, 5.3; 95% CI, 2.4-11.9) [5]. In contrast to these findings, in a cohort of 389 women with RM, no JAK2V617F mutations were observed (0.0%; 95% CI, 0-0.009%) [6]. In view of these discordant data, we aimed to assess prevalence of the JAK2V617F mutation in a well-defined group of women with unexplained RM.We included consecutive women who consulted our recurrent miscarriage clinic between October 2005 and November 2007 at the Academic Medical Center, Amsterdam. Women were eligible if aged between 18 and 42 years and diagnosed with unexplained RM. RM was defined as two or more miscarriages with an upper gestational age of 20 weeks. All women were investigated according to a standardized local protocol (derived from the Dutch guidelines on RM) [7]. Unexplained RM was diagnosed in the case of normal parental karyotypes of both partners, the absence of uterine pathology on pelvic ultrasound, absence of antiphospholipid syndrome (lupus anticoagulant and anticardiolipin IgG and IgM), and a normal fasting level of homocysteine (lower than 16 lmol L )1). Participating women were tested for inherited thrombophilia, but the presence of factor V Leiden, the prothrombin 20210A mutation, or deficiencies of antithrombin, protein C or S, were not considered an explanation for RM.DNA was isolated from peripheral blood using standar...