Hawkins J R
Hum Mutat. 1993;2(5):347-50. doi: 10.1002/humu.1380020504.
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.
在寻找哺乳动物睾丸决定因子（TDF）的过程中，发现了位于Y染色体上的基因SRY（性别决定区Y基因）。将SRY评估为TDF候选基因的方法包括，在睾丸发育失败的患者（XY女性或46,XY性腺发育不全）基因组中发现SRY的突变，以及产生携带SRY小鼠同源基因[Sry]的转基因性逆转雌性小鼠。自从最初利用XY女性来证明SRY/TDF的一致性以来，已经使用不同技术分析了更多患者，并鉴定出更多突变。现已描述了SRY中的总共11种突变，均位于该基因的DNA结合HMG盒区域，且均存在于明显完全性腺发育不全的患者中。令人惊讶的是，已鉴定出三种家族性SRY突变，其表型为可育男性或不育性逆转女性。SRY突变的XY女性比例估计平均约为15%。XY性逆转中SRY突变频率较低的原因可能是SRY尚未发现区域存在突变、发生了产生相同表型的突变（可能在睾丸决定途径中靠近SRY的基因中），或者对完全性腺发育不全的诊断错误。
