Genetic Investigation of Patients with 46,XX Testicu-lar Disorder of Sex Development

Background: 46,XX Testicular Disorder of sex development (46,XX Testicular DSD) is a rare disease with 1/60000 birth incidence. These patients are characterized by 46,XX karyo-type, testicular gonads, male external genitalia, male gender identification, hyper gonadotropic hypogonadism, and azoo-spermia. Some of these patients can be diagnosed at birth or early life because of penile abnormalities, but in some cases, there is no evidence of abnormalities in their genitals, there-fore they are referred to the clinic due to puberty disorders or infertility. Most of these patients do not have any molecular diagnosis.Materials and Methods: In the collaboration of Royan institute with Endocrinology and Metabolism Research Center of Teh-ran University, 326 patients referred due to infertility, or genital abnormalities, have been nominated for this study. Karyotype has been performed on their peripheral blood to investigate chromosomal abnormalities. Patients with 46,XX karyotype and male phenotype underwent PCR based SRY gene analysis to determine the presence of this gene in their genome. In order to analysis genetic variations, upstream region of SOX9, and SOX3, and exon 4 of NR5A1, and RSPO1 were selected.Results: 66 patients had 46,XX karyotype with female pheno-type, and 46,XX SRY-Negative has been observed in 5 patients. Genetic variations on the candidate genes were not observed in the patients’ samples.Conclusion: This study indicated that there is a large number of patients with unknown etiology which their samples should undergone Whole Exome Sequencing for better understanding of their genomic status.

کلیدواژه ها:

46 ، XX Testicular DSD ، Disorders of Sex Develop-ment ، Ambiguous Genitalia ، Sex Reversal ،