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 th e finding of mutations in SRY in the genomes of patients with failed t estis development (XY females or 46,XY gonadal dysgenesis) and the pro duction of female to male sex reversed mice transgenic for the mouse h omologue of SRY, [Sry]. Since the initial use of XY females in the pro of of SRY/TDF identity, many more patients have been analysed using di fferent techniques and more mutations identified. A total of 11 mutati ons in SRY have now been described, all in the DNA-binding HMG-box reg ion of the gene, and all in patients with apparently complete gonadal dysgenesis. Surprisingly, three familial SRY mutations have been ident ified, where the phenotype is either fertile male or sterile sex-rever sed female. Estimates of the proportion of XY females mutant for SRY a verage at approximately 15%. Reasons for the low frequency of SRY muta tions 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 determinin g pathway, or incorrect diagnosis of complete gonadal dysgenesis. (C) 1993 Wiley-Liss, Inc.