Molecular analysis of SRY gene in Brazilian 46, XX sex reversed patients: absence of SRY sequence in gonadal tissue

Background: The importance of the Y chromosome in male determination has been well established for a long time. The presence of a translocation of chromosomal material encoding the Testis-Determining Factor from Y to another chromosome has been one of the hypothesis to explain testicular development in XX sex-reversed patients. Material and methods: In the present study, we searched for SRY sequence in genomic DNA isolated from peripheral leukocytes in eleven 46, XX true hermaphrodites and four 46, XX males (only one with ambiguous genitalia). We also analyzed the presence of SRY sequence in fresh gonadal tissues from two 46, XX true hermaphrodites. Results: SRY sequence was absent in DNA blood samples of all true hermaphrodites and in testicular and ovarian tissues of two cases studied. Of the four 46, XX males, two with normal male external genitalia were SRY positive. Conclusions: We did not identify the SRY gene in 46, XX true hermaphrodites and 46, XX males with ambiguous genitalia, therefore SRY translocation to X chromosome or autosome is unlikely. Hidden Y mosaicism in gonadal tissues was also ruled out in two cases, suggesting that cryptic SRY mosaicism in gonadal tissues is not the usual mechanism responsible for testicular development in patients with 46, XX true hermaphroditism. However, SRY gene was identified in two 46, XX males with male external genitalia showing that SRY gene determined their male phenotype. Despite the recent advances in the knowledge of the role of several genes involved in sexual determination we are still unable to explain the cause of most of Y-chromosome-negative 46, XX sex-reversed patients.