Genetic Etiology of 46, XY Disorders of Sex Development in Chinese Patients: Insights From Whole-Exome Sequencing.

This study investigated genetic causes of 46, XY DSD in 134 Chinese patients via whole-exome sequencing (WES). Clinical data analysis identified 86 rare variants (14 novel, 72 recurrent) across 46, XY DSD-related genes. Following ACMG guidelines, 71 variants were classified as pathogenic/likely pathogenic (P/LP). Affected genes were linked to androgen production/function (63 variants), testicular development (19), and syndromic forms (4). SRD5A2, AR, and NR5A1 emerged as the most frequent causative genes, accounting for ~90% of cases. Novel variants in 11 genes expanded the genetic spectrum, offering insights into underlying mechanisms and improving diagnostic precision. These findings enhance understanding of 46, XY DSD pathogenesis and underscore WES's utility in resolving diagnostic challenges for improved clinical management.