Identification of new variants of the BMP15 gene causing Premature Ovarian Failure in Lorestan families by whole-exome sequencing and In silico analysis

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.