Absence of Pathogenic INSR Variants p.Arg1201Trp and p.Phe409Val in Ovarian Granulosa Cells of Iranian Women with Polyendocrine Metabolic Ovarian Syndrome

Abstract

Background: Polyendocrine metabolic ovarian syndrome (PMOS) is a common endocrine disorder with a strong genetic component and is frequently associated with insulin resistance. The insulin receptor gene (INSR) is a leading candidate gene; however, data on rare pathogenic INSR variants in ovarian tissue are limited. Objectives: This study aimed to determine whether two previously reported pathogenic INSR variants, p.Arg1201Trp and p.Phe409Val, are detectable in granulosa cells obtained from Iranian women with PMOS. Methods: Granulosa cells were isolated from the ovarian follicles of 40 women with PMOS and 40 healthy controls undergoing in vitro fertilization (IVF). DNA was extracted, and the target loci were genotyped using high-resolution melting (HRM) curve analysis, followed by Sanger sequencing for confirmation. Results: All participants (100%) were homozygous for the wild-type allele at both loci, p.Arg1201Trp (c.3601C>T) and p.Phe409Val (c.1225T>G); no heterozygous or mutant genotypes were detected by HRM or by Sanger sequencing. Conclusions: The absence of these variants suggests that they are not a common cause of PMOS in this cohort, underscoring the need for comprehensive genomic analyses of the entire INSR gene and other components of the insulin-signaling pathway.