NS Fatemi - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Department of Genetics and Molecular Medicine, School of Medi-cine, Zanjan University of Medical Sciences (ZUMS), Zanjan,
F Ray Pierre - Genetic Epigenetic and Therapies of Infertility, Institute for Ad-vanced Biosciences, University of Grenoble, Alpes, France.. UF de Biochimie Génétique et Moléculaire, Grenoble, France
A Amiri-Yekta - Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
F Ramezanali - Department of Endocrinology and Female Infertility, Reproduc-tive Biomedicine Research Center, Royan Institute for Reproduc-tive Biomedicine, ACECR, Tehran, Iran

Background: Recurrent pregnancy loss (RPL) is a multifacto-rial disorder and defined as two or more consecutive miscar-riages that affects up to 5% of clinical pregnancies. Several factors are associated with RPL, however, in 35–60% of mis-carriages the etiology remains unexplained. In recent years, the advent of high throughput technologies, such as next generation sequencing (NGS), have provided new capabilities for discov-ery of too small genetic changes in hereditary diseases such as RPL. In this study, we used whole-exome sequencing approach (WES) to find pathogenic variants in an Iranian family with RPL history.Materials and Methods: After finding an affected family, clinical investigations were done. Genomic DNA was extract-ed from blood samples and qualified and quantified DNA was subjected to WES. DNA sequencing was done by HiSeq 2000 from Illumina®, and the reads were aligned to the human ref-erence genome (hg19). After variant calling and filtering, the variations that scored as ‘tolerated’ and ‘benign’ were excluded. And at the end, a candidate variant was confirmed by sanger sequencing method in family members.Results: Clinical investigations such as thrombophilia’s, uter-ine anatomy, hormonal /endocrine disorders, immunologic fac-tors, infections, karyotyping and Microarray-based compara-tive genomic hybridization (array CGH) in the proband were normal. A new missense mutation was identified in 100% ana-lyzed subjects with RPL history.Conclusion: In conclusion, to our knowledge, this is the first study investigating genetic variations in RPL through a family-based exome sequencing which found a new mutation in 3 outof 3 (100%) RPL patients. Our results expand our knowledge on the involvement of a new gene in human pregnancy com-plications. Indeed, our findings confirm that WES is a useful alternative approach to reach a genetic diagnosis in patients.

Recurrent Pregnancy Loss, Next Generation Se-quencing, Whole Exome Sequencing