GENETIC-HETEROGENEITY AND PHENOTYPIC VARI ABILITY IN 46,XY SEX REVERSAL

The discordance between the chromosomic and the gonadal-phenotypic sex is known as sex reversal (XX males and XY females). We review the XY pure gonadal dysgenesis characterized by female phenotype, primary ame norrhea and absence of secondary sexual development. Bilateral streak gonads are always present in the complete form of this syndrome, while variable degrees of virilization are found in the partial forms, depe nding on the severity of the testicular damage. A plausible explanatio n for this pathology are SRY mutations that interfere with the testicu lar differentiation. However, only 10-15% of the patients with the com plete form show SRY mutations, particularly in the HMG box. The remain ing cases are probably due to mutations in different autosomal or X-li nked genes which are also involved in the sex differentiation cascade. Recently, it has been shown that mutations in several genes responsib le of well known genetic entities as WT1, SOX9, DSS and SF1, result.in sex reversal. These findings reveal the genetic heterogeneity and cli nical variability of XY sex reversal and provide the basis establishin g a hierarchy of genes and their participation in the sex determinatio n pathway.