Exploring the clinical implications of novel SRD5A2 variants in 46,XY disorders of sex development

This study analyzed 68 patients with SRD5A2 deficiency and 46,XY disorders of sex development, identifying 28 SRD5A2 variants, including seven novel mutations primarily in exon 1 and exon 4. The study found that these novel variants may interfere with NADPH binding and destabilize protein structure, contributing to the disorder's pathogenic mechanisms. The external genitalia scores of 53 patients who underwent surgery varied, with a mean score of 6.8, and hormone testing in 30 patients revealed an average testosterone-to-dihydrotestosterone ratio of 49.3. The research expands the SRD5A2 variant database, aiding in the development of diagnostic and therapeutic strategies for SRD5A2 deficiency.