Identification of new variants of the BMP15 gene causing Premature Ovarian Failure in Lorestan families by whole-exome sequencing and In silico analysis
DOI:
https://doi.org/10.5281/zenodo.17066905Keywords:
Premature ovarian insufficiency (POI), , BMP15, infertility, whole-exome sequencingAbstract
Premature ovarian insufficiency (POI) is characterized by the halt of ovarian function prior to the age of 40, presenting with diminished sex hormone levels, elevated gonadotropin levels, and resulting in infertility and recurrent miscarriages in females. Genetic elements contribute significantly to the reproductive challenges associated with POI, impacting both infertility and miscarriage occurrences. A key player in folliculogenesis, BMP15, a TGFβ superfamily member, governs this pathway and any alterations in its gene sequence can disrupt normal follicle development. BMP15, expressed in oocytes, is pivotal for reproductive processes in certain species. When POI manifests, disruptions in BMP15 gene function result in infertility, escalating the likelihood of miscarriages due to compromised oocyte quality and diminished ovarian reserves.
Genomic DNA was extracted from the peripheral blood sample after a physical examination, ultrasound. Whole Genome Sequencing were performed. In silico prediction tools utilized were Phyer-2 web server, Polymorphism Phenotyping version 2 (PolyPhen-2), GalaxyWEB and ModRefiner, UCSF Chimera software, molecular docking using ClusPro 2.0.
Exome sequencing revealed a missense mutation c.226C>T:p.Arg76Cys in exon 1 of the BMP15 gene in Lorestan families. In silico prediction tools revealed that variation Arg 76 Cys changed the binding affinity and pattern of the BMP-15 and BMPR1B complex. Changes in the binding affinity and pattern of the complex protein may cause disruptions in BMP15 gene function and can lead to infertility.
The identification of BMP15 gene variants holds promise for healthcare practitioners to devise more targeted interventions, potentially ameliorating the impact of infertility and miscarriage among affected individuals. Hence, this investigation delves into exploring BMP15 gene variations within a cohort of infertile women from Lorestan province grappling with premature ovarian insufficiency
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