Extended genotype-phenotype spectrum of 17α-hydroxylase/17,20-lyase deficiency: a nine-case series featuring a novel mutation, suspected TART-like lesions, and multisystem involvement.

Context: 17α-hydroxylase/17,20-lyase deficiency (17-OHD), a rare congenital adrenal hyperplasia driven by biallelic CYP17A1 variants, shows extensive clinical and molecular heterogeneity; data on rare phenotypes and genotype-phenotype patterns are scarce. Objective: To characterize clinical, hormonal, gonadal pathological, and genetic features of nine Chinese patients with 17-OHD from a single center, expand the population-specific CYP17A1 variant spectrum, explore genotype-subtype trends, and document rare incidental manifestations to inform clinical care and genetic counseling. Methods: A retrospective case series included nine genetically verified patients (seven 46,XY, two 46,XX). SWISS-MODEL homology modeling and American College of Medical Genetics and Genomics (ACMG) criteria were applied to assess the novel variant's pathogenicity. Results: The homozygous c.985_987delTACinsAA (p.Y329Kfs Conclusions: This cohort extends the Chinese pathogenic CYP17A1 variant spectrum and reveals tentative genotype-subtype associations plus rare co-occurring phenotypes. Larger multicenter cohorts and functional experiments are needed to validate causal links between atypical manifestations and 17-OHD. Early adrenal steroid profiling and CYP17A1 sequencing are recommended for patients with hypertension, hypokalemia, and disorders of sex development. Serial ovarian reserve testing is required for 46,XX patients, and long-term gonadal imaging follow-up for 46,XY patients with gonadal dysgenesis.