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

Mandana Rastari; Masomeh Askari; Kenneth McElreavey; Anu Bashamboo; Zeinab Rokhsattalab; Maryam Razzaghy-Azar; Mahdieh Bakhshi; Mehdi Totonchi

doi:10.1515/jpem-2024-0352

Article

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

Mandana Rastari , Masomeh Askari , Kenneth McElreavey , Anu Bashamboo , Zeinab Rokhsattalab , Maryam Razzaghy-Azar , Mahdieh Bakhshi and Mehdi Totonchi

Published/Copyright: January 21, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 3

Abstract

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.

Keywords: gonadal dysgenesis; sex determination; disorders of sex development; ambiguous genitalia

Corresponding author: Mehdi Totonchi, Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran, E-mail: totonchimehdi@gmail.com

Acknowledgments

The authors thank all the patients and families who contributed samples to this project and consented to have their data shared.

Research ethics: This study was performed in line with the principles of the Declaration of Helsinki for medical research involving human subjects. Approval was granted by the Ethics Committee of the Royan Institute, Tehran, Iran (IR.ACECR.ROYAN.REC.1398.130).
Informed consent: Informed consents were obtained from the patients or their legal guardians.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine: Grammarly, an AI-powered tool, was used to improve the language and writing quality of the manuscript. The use of this tool was carefully reviewed and approved by the authors and did not compromise the integrity of the research process.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The data that support the findings of this study are available upon reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jpem-2024-0352).

Received: 2024-07-25

Accepted: 2025-01-06

Published Online: 2025-01-21

Published in Print: 2025-03-26

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Keywords for this article

gonadal dysgenesis; sex determination; disorders of sex development; ambiguous genitalia