CANDIDATE GENES IN COMPLETE AND PARTIAL XY SEX REVERSAL - MUTATION ANALYSIS OF SRY, SRY-RELATED GENES AND FTZ-F1

The sexual phenotype is established in three steps: (1) the sex chromo some constitution; (2) the differentiation of the gonads; and (3) the response of the internal and external genitalia to the hormones produc ed by the differentiated gonads. Errors that occur at any of these sta ges can result in defective sexual differentiation. Therefore the inve stigation of patients with abnormalities of testis development will he lp elucidate the mechanisms of sex determination and gonadal different iation. It was in this way that SRY, the primary testis determining ge ne was identified. De novo mutations in SRY, result in gonadal dysgene sis by disrupting the DNA-binding activity of the SRY protein. However , only 20% of cases of gonadal dysgenesis, are explained by mutations in SRY or its flanking sequences. Therefore, there are several pieces to this puzzle yet to be discovered and it is hoped that mutation anal ysis of other genes implicated in gonadal development and differentiat ion may shed some light on aetiology of gonadal dysgenesis in the rema ining 80% of cases. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.