Cytogenetic and molecular characterization of four patients with differences in sexual development

Abstract

Differences in sexual development (DSD) encompass a diverse spectrum of conditions arising from alterations during fetal development related to genetic, gonadal, or phenotypic sex. With a prevalence of less than 1 case per 2,000 newborns, these entities are classified as rare diseases. The objective was to characterize four patients with differences in sexual development through cytogenetic and molecular analysis in order to establish genotype-phenotype correlations. Four patients were evaluated due to presenting reproductive disorders. Lymphocyte cultures with GTG-banding were performed, complemented by fluorescence in situ hybridization (FISH) using X-centromeric and SRY gene locus-specific probes. Additionally, SRY gene detection was carried out using polymerase chain reaction (PCR). Three patients with a male phenotype presented a 46,XX karyotype and the presence of the SRY gene, suggesting a translocation of the SRYlocus to the X chromosome during paternal meiosis. One patient with a female phenotype exhibited a 46,XY karyotype and the absence of the SRY gene. Distinct phenotypic peculiarities were observed in the patients consistent with their respective diagnoses. The integration of cytogenetic techniques (karyotype + FISH) and molecular methods (SRYdetection) is fundamental for the accurate diagnosis of these entities. These findings not only help elucidate underlying genetic mechanisms but also guide personalized genetic counseling strategies, minimizing clinical uncertainty for affected families.