Clinical Exome Sequencing Unveils the Genetic Landscape of Polycystic Ovarian Syndrome Focusing on Lean and Obese Phenotypes: Implications for Cost-Effective Diagnosis and Personalized Treatment

This study investigates the genetic basis of PCOS in both lean and obese individuals using clinical-exome sequencing. A total of 26,550 variants were identified, with 5170 common and 2232 and 2322 unique to lean and obese phenotypes, respectively. Key findings include the significant roles of leptin signaling impairment, insulin resistance, and mutations in genes such as CYP1A1, CYP19A1, ESR1, AR, AMH, AdipoR1, NAMPT, NPY, PTEN, EGFR, and Akt. The study concludes that young women in West Bengal, India, are more likely to have co-occurring PCOS with estrogen resistance, leptin receptor insufficiency, folate deficiency, T2DM, and acanthosis, with obesity being a common phenotypic expression.