Novel genes and mutations in patients affected by recurrent pregnancy loss
Suarez Martinez, Carlos Fernando
Alfonso Patarroyo, Manuel
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. © 2017 Quintero-Ronderos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fibrinogen ; Secondary ; Stromelysin 2 ; Habitual ; Habitual ; Human ; Molecular ; Fibrinogen ; Fibrinogen Alphac ; Mmp1 Protein ; Peptide Fragment ; Stromelysin 2 ; Adamts1 Gene ; Amn Gene ; Bioinformatics ; Bmp7 Gene ; Caucasian ; Cdh1 Gene ; Cdh11 Gene ; Clinical Article ; Col6A3 Gene ; Cr1 Gene ; Dna Modification ; Epas1 Gene ; F5 Gene ; Fga Gene ; Fgfr2 Gene ; Flt1 Gene ; Gene ; Gene Function ; Gene Mutation ; Gene Sequence ; Genetic Code ; Genetic Stability ; Genetic Variability ; Genetic Variation ; Human ; Ido2 Gene ; Lifr Gene ; Mmp1 Gene ; Mmp9 Gene ; Ncoa1 Gene ; Next Generation Sequencing ; Phenotype ; Recurrent Abortion ; Sanger Sequencing ; Thbd Gene ; Tlr3 Gene ; Tnc Gene ; Traf3Ip1 Gene ; Tro Gene ; Whole Exome Sequencing ; Abortion ; Biology ; Chemistry ; Exome ; Gene Expression ; Genetics ; Genotype ; High Throughput Sequencing ; Metabolism ; Molecular Model ; Mutation ; Pathophysiology ; Pregnancy ; Protein Domain ; Protein Secondary Structure ; Quantum Theory ; Thermodynamics ; Abortion ; Computational Biology ; Exome ; Fibrinogen ; Gene Expression ; Genotype ; High-Throughput Nucleotide Sequencing ; Matrix Metalloproteinase 1 ; Models ; Mutation ; Peptide Fragments ; Phenotype ; Pregnancy ; Protein Interaction Domains And Motifs ; Protein Structure ; Quantum Theory ; Thermodynamics ;
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