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

摘要

BACKGROUND: The importance of the Y chromosome in male determination hasbeen well established for a long time. The presence of a translocation of chromosomal material encodingthe Testis-Determining Factor from Y to another chromosome has been one of the hypothesis to explaintesticular development in XX sex-reversed patients. MATERIAL AND METHODS: In the present study, we searchedfor SRY sequence in genomic DNA isolated from peripheral leukocytes in eleven 46,XX true hermaphroditesand four 46,XX males (only one with ambiguous genitalia). We also analyzed the presence of SRY sequencein fresh gonadal tissues from two 46,XX true hermaphrodites. RESULTS: SRY sequence was absent in DNAblood 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 didnot identify the SRY gene in 46,XX true hermaphrodites and 46,XX males with ambiguous genitalia, thereforeSRY translocation to X chromosome or autosome is unlikely. Hidden Y mosaicism in gonadal tissues wasalso ruled out in two cases, suggesting that cryptic SRY mosaicism in gonadal tissues is not the usualmechanism 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 determinedtheir male phenotype. Despite the recent advances in the knowledge of the role of several genes involvedin sexual determination we are still unable to explain the cause of most of Y-chromosome-negative 46,XXsex-reversed patients.