Mutational analysis of SRY in XY females

The Y chromosome located gene SRY (sex determining region Y gene) was identified in the search for the mammalian testis determining factor ( TDF ). Approaches for evaluating SRY as a candidate for TDF included the finding of mutations in SRY in the genomes of patients with failed testis development (XY females or 46, XY gonadal dysgenesis) and the production of female to male sex reversed mice transgenic for the mouse homologue of SRY , [ Sry ]. Since the initial use of XY females in the proof of SRY / TDF identity, many more patients have been analysed using different techniques and more mutations identified. A total of 11 mutations in SRY have now been described, all in the DNA‐binding HMG‐box region of the gene, and all in patients with apparently complete gonadal dysgenesis. Surprisingly, three familial SRY mutations have been identified, where the phenotype is either fertile male or sterile sex‐reversed female. Estimates of the proportion of XY females mutant for SRY average at approximately 15%. Reasons for the low frequency of SRY mutations in XY sex reversal could be the presence of mutations in regions of SRY not yet discovered, the occurrence of mutations that give the same phenotype, perhaps in genes close to SRY in the testis determining pathway, or incorrect diagnosis of complete gonadal dysgenesis. © 1993 Wiley‐Liss, Inc.