A small Mexican study looked at DNA changes in the kisspeptin‑related KNDy pathway to see if they cause early ovarian failure. They found a few genetic variants, but these were just as common in healthy women, meaning the variants probably don’t cause the condition. So testing these genes isn’t helpful for diagnosing or treating early ovarian loss.

Previous studies have demonstrated the essential role of the Kisspeptin/Neurokinin B/Dynorphin A (KNDy) pathway in female reproductive biology by regulating the activity of the hypothalamic-pituitary-gonadal axis. Identified loss-of-function mutations in these genes are linked to various reproductive disorders. This study investigated genetic disorders linked to mutations in the <i>KNDy</i> genes related to premature ovarian insufficiency (POI). A cohort of 14 Mexican POI patients underwent genetic screening using PCR-SSCP and Sanger sequencing, assessing the genetic variations' impact on protein function thereafter using multiple in silico tools. The PCR excluded extensive deletions, insertions, and duplications, while SSCP detected five genetic variants. Variations occurred in the <i>KISS1</i> (c.58G&gt;A and c.242C&gt;G), <i>KISS1R</i> (c.1091A&gt;T), <i>PDYN</i> (c.600C&gt;T), and <i>OPRK1</i> (c.36G&gt;T) genes, whereas no genetic anomalies were found in <i>NK3/NK3R</i> genes. Each single-nucleotide variant underwent genotyping using PCR-SSCP in 100 POI-free subjects. Their allelic frequencies paralleled the patient group. These observations indicate that allelic variations in the <i>KNDy</i> genes may not contribute to POI etiology. Hence, screening for mutations in <i>KNDy</i> genes should not be a part of the diagnostic protocol for POI.