Abstract
PURPOSE: This study aimed to investigate the genetic etiology in an infertile patient presenting with consistently elevated progesterone levels. METHODS: Genomic DNA was extracted from the patient's blood sample and subjected to whole-genome sequencing (NGS) using the Illumina NovaSeq platform. Bioinformatic analyses were conducted to identify single nucleotide variants (SNVs) and insertion-deletion mutations (Indels) potentially associated with the patient's clinical phenotype. These variants were subsequently validated using Sanger sequencing. To further assess the functional implications of these genetic variants, three-dimensional protein structure simulations and substrate molecular docking analyses were performed on the variant proteins. RESULTS: A point mutation, c.1096 G > T (p.Val366Leu), was identified in the patient's CYP17A1 gene. Compared to the wild type, the mutant exhibited no significant changes in the overall or local three-dimensional structure, and molecular docking analysis showed no notable difference in binding energy. A literature review indicated that this mutation site is located in the region where the CYP17A1 enzyme interacts with cytochrome b5 (Cyt b5). CONCLUSIONS: We report, for the first time, that a novel mutation in the CYP17A1 gene in an infertile woman may have led to isolated 17,20-lyase deficiency. The patient successfully achieved pregnancy and delivered a healthy baby through in vitro fertilization (IVF).