KHDC3L frame-shift mutation causes recurrent pregnancy loss and infertility in an Iranian family

Background: Recurrent pregnancy loss (RPL) is a common infertility-related disease affecting about 1-3% of women worldwide. The parental and embryo different conditions have been associated with RPL. However, it has been estimated that approximately half of cases remains unexplained.Objective: In recent years, next generation sequencing technology, acts as a robust tool to discovery of causal mutations in hereditary diseases such as RPL.Materials and Methods: In this study, we recruited an Iranian family with RPL history by whole-exome sequencing approach. Then, the effect of selected candidate pathogenic variant was confirmed using Sanger sequencing method in family members.Results: Clinical investigations such as thrombophilias, uterine anatomy, hormonal/endocrine disorders, immunologic factors, infections and karyotyping in proband were normal. KHDC3L mutation was identified in 50% and 100% analyzed subjects with RPL and hydatidiform mole (HM) history, respectively.Conclusion: In conclusion, the results, for the first time, indicated that the detected variant in KHDC3L gene is involved not only in the HM but can also contribute to RPL that is in contrast with previous studies. Therefore, our findings confirm that WES is a useful alternative approach to Sanger sequencing to reach a genetic diagnosis in patients.

Keywords:

Recurrent pregnancy loss , Whole exome sequencing , KHDC3L , Hydatidiform mole