Molecular analysis in true hermaphroditism

Abstract

A true hermaphrodite (TH) is defined as an individual in whom both testicular and ovarian tissues are present. The diagnosis must be made histologically. The typical karyotype is 46,XX but about 30% of patients are chimeras 46,XX/46,XY. A small percentage of TH are 46,XY. Six documented histologically cases of TH have seen in the de Medical Genetic Unit of University of Zulia, Maracaibo, Venezuela, since 1985 to 1997. A molecular investigation was undertaken in an attempt to determine the cause of this disorder. Y-specific sequences, including SRY gene, were analyzed through polymerase chain reaction, single strand conformational polymorphism and direct sequencing. Three patients showed positive Y-sequences (two with 46,XX/46,XY and one with 46,XY karyotypes). These three patients did not have mutations in the amplified SRY fragments. In other three patients (46,XX karyotype), Y-sequences were shown to be absent from lymphocytes, genital skin fibroblasts or ovarian and testicular components of both ovotestes. Our data demonstrate that this phenotype does not always correlate with the presence or absence of Y-sequences in the genome, and confirm that TH is a genetically heterogeneous condition, suggesting that other genes working independently of SRY may also determine testicular differentiation.