Functional Evaluation of Novel CYP21A2 Variants: Expanding the Genetic Basis of Non-Classic CAH

This study investigates the pathogenicity of novel CYP21A2 variants in relation to non-classic congenital adrenal hyperplasia (NC-CAH), a genetic disorder affecting hormone production. The research involved analyzing mutations from patients with NC-CAH symptoms and additional variants from SNP databases. The study found that certain mutations, such as A81T, R125G, I161T, and L289H, significantly impair protein structure and reduce enzyme activity, contributing to NC-CAH phenotypes. These findings enhance the understanding of NC-CAH and could improve diagnosis and treatment strategies, potentially mitigating severe outcomes like miscarriages or irreversible alopecia. The study also highlights the importance of awareness among heterozygous carriers for family planning and medical decisions.