Investigation of associated single gene mutations in couples with recurrent pregnancy losses

In couples with recurrent pregnancy loss (≥2), the aetiology can be explained in approximately 50% by using traditional tests for known causative factors. In this study, we have investigated the women, with ≥3 fetal losses and without known genetic/nongenetic factors, by 'Whole Exome Sequencing (WES)' technique to determine the effect of monogenic disorders. At first, clinical records of 973 cases, who were referred to the outpatient clinic of Medical Genetics Department of Istanbul Medical Faculty, Istanbul University are evaluated retrospectively. From the couples with normal cytogenetic and other traditional test results, women are selected and informed about the study. The women who gave written consent (n:35) are included. Wet-laboratory work of WES was carried out with service provider. Analyses of variants involved in different pathways, including their confirmations and segregations are performed in our laboratory. Ninety-three variants with possible associations have been observed in 34 cases. In two of those cases, the aetiology is determined (5.7%), while in 18 (51.4%), admittance of other family members (husbands, sisters, and mothers) are planned to expand the segregations. Functional studies are also planned to clarify the effect of variants in 10 cases (28.5%). Polygenic inheritance has been proposed in seven cases (20%). Variants found in this study were divided according to the pathways such as metabolism (n=8), cilia activity (n=8) and embryogenesis (n=7); providing cell division (n=5), oocyte maturation and development (n=6) and fetomaternal communication in the early stages of pregnancy (n=8). According to best of our knowledge, this is third international and first national series sharing the WES results in women with recurrent pregnancy losses.