Clinical and genetic diagnosis of first cohort of differences of sexual development in the Iranian population.

Objectives: Differences of sex development (DSD) refer to various congenital conditions affecting the urogenital and hormonal systems. Accurate diagnosis and personalized management are crucial for supporting patients through complex decisions, such as those related to gender identity.

Methods: This study represents the first comprehensive investigation into DSD in Iran, analyzing patient's clinical and genetic data between 1991 and 2020. Karyotype analysis was performed on 69 patients without a molecular diagnosis, with sex chromosome DSD excluded. Presence of SRY gene evaluated in all sex reversal patients. Whole exome sequencing (WES) was used for 26 undiagnosed patients, revealing pathogenic variants in WT1, NR5A1, DHX37, AR, CYP17A1, and LHCGR genes.

Results: The most common diagnosis was testicular TDSD, identified in 42 patients (60.86 %), with the SRY gene being the primary cause in 36 of these patients. The study highlights the importance of genetic analysis in identifying novel and rare gene variants, particularly within the steroid hormone and gonad differentiation pathways, for both 46, XY and 46, XX DSD.

Conclusions: These findings emphasize the need for genetic analysis in providing personalized patient care and tailored counseling to help individuals navigate complex decisions, including those involving gender identity.