Novel genes and mutations in patients affected by recurrent pregnancy loss

Paula Quintero-Ronderos, Eric Mercier, Michiko Fukuda, Ronald González, Carlos Fernando Suárez, Manuel Alfonso Patarroyo, Daniel Vaiman, Jean-Christophe Gris, Paul Laissue

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Recurrent pregnancy loss is a frequently occurring human infertility-related disease affecting ~1% of women. It has been estimated that the cause remains unexplained in >50% cases which strongly suggests that genetic factors may contribute towards the phenotype. Concerning its molecular aetiology numerous studies have had limited success in identifying the disease's genetic causes. This might have been due to the fact that hundreds of genes are involved in each physiological step necessary for guaranteeing reproductive success in mammals. In such scenario, next generation sequencing provides a potentially interesting tool for research into recurrent pregnancy loss causative mutations. The present study involved whole-exome sequencing and an innovative bioinformatics analysis, for the first time, in 49 unrelated women affected by recurrent pregnancy loss. We identified 27 coding variants (22 genes) potentially related to the phenotype (41% of patients). The affected genes, which were enriched by potentially deleterious sequence variants, belonged to distinct molecular cascades playing key roles in implantation/pregnancy biology. Using a quantum chemical approach method we established that mutations in MMP-10 and FGA proteins led to substantial energetic modifications suggesting an impact on their functions and/or stability. The next generation sequencing and bioinformatics approaches presented here represent an efficient way to find mutations, having potentially moderate/strong functional effects, associated with recurrent pregnancy loss aetiology. We consider that some of these variants (and genes) represent probable future biomarkers for recurrent pregnancy loss.

Original languageEnglish (US)
Pages (from-to)e0186149
JournalPLoS One
Issue number10
StatePublished - 2017
Externally publishedYes

Cite this

Quintero-Ronderos, P., Mercier, E., Fukuda, M., González, R., Suárez, C. F., Patarroyo, M. A., Vaiman, D., Gris, J-C., & Laissue, P. (2017). Novel genes and mutations in patients affected by recurrent pregnancy loss. PLoS One, 12(10), e0186149.