Cytogenetic and molecular characterization in gonadal tissue of patients with ovotesticular syndrome and gonadal dysgenesis 46,XY and 46,XX

Objectives: The etiology of gonadal dysgenesis and the ovotesticular syndrome is unknown in most cases. The aim of the study was to perform cytogenetic and molecular characterization of a group of patients with ovotesticular syndrome and complete gonadal dysgenesis from peripheral blood and gonadal tissue samples. Materials and methods: A total of 6 patients were included, 3 with 46,XX ovotesticular syndrome diagnosis, 1 diagnosed with 46,XY ovotesticular syndrome; 1 suspected with 46,XX gonadal dysgenesis, and 1 with 46,XY complete gonadal dysgenesis. Results: All patients were evaluated with karyotype, fluorescence in situ hybridization (FISH) for SRY, multiplex ligation-dependent probe amplification (MLPA) and comparative genomic hybridization (aCGH) in peripheral blood samples. In cases with available gonadal tissue, the levels of genetic expression of SOX3, SRY, and SOX9 were determined by real-time PCR and immunofluorescence. Rearrangements involving SRY gene were ruled out. No deletions/duplications or copy-number variations (CNVs) were identified as the etiology for the sexual development disorder in any of the studied patients. In one case of 46,XX ovotesticular syndrome, the gonadal karyotype was different from the karyotype in peripheral blood. Aberrant expression of SOX3 and SOX9 in gonadal tissue was observed in one case of 46,XX ovotesticular syndrome. Conclusions: Lower levels of SRY and SOX9 expression were documented in the gonadal tissue of a case of 46,XY ovotesticular syndrome, in commparison with the levels in human cellular lines of embryonic testicle and Sertoli cells. Cytogenetic and molecular studies of gonads complementary to peripheral blood studies have the potential of enhancing the understanding of sexual development disorders in patients who are XX or XY in peripheral blood.