SRY

Variants (also called mutations) in the SRY gene have been identified in approximately 15 percent of individuals with Swyer syndrome, also known as 46,XY complete gonadal dysgenesis or 46,XY pure gonadal dysgenesis. Swyer syndrome is a condition that affects sex development. Individual with this condition have a male-typical chromosome pattern (46,XY karyotype), but they develop female-typical sex characteristics. 

SRY gene variants that cause Swyer syndrome prevent production of the sex-determining region Y protein or result in the production of a nonfunctioning protein. Without functional sex-determining region Y protein, a fetus will not develop testes but will develop a uterus and fallopian tubes, despite having an X and a Y chromosome.

Changes affecting the SRY gene have been found to cause 46,XX testicular difference of sex development. Individuals with this condition have a female-typical chromosome pattern (46,XX karyotype) but develop male sex characteristics, including testes, though they may be small and undescended. 

In most individuals with 46,XX testicular difference of sex development, the condition results from an abnormal exchange of genetic material  (translocation) between the Y chromosome and another chromosome, most often the X chromosome. This exchange occurs as a random event during the formation of sperm cells in the affected person's father. In this condition, the SRY gene (which is on the Y chromosome) is misplaced, almost always onto an X chromosome. A fetus with an X chromosome that carries the SRY gene will develop male sex characteristics despite not having a Y chromosome.

SRY gene variants  that impair the function of the sex-determining region Y protein have been identified in a small number of people with 46,XY difference of sex development, or partial gonadal dysgenesis. The effects of these variants on the function of the sex-determining region Y protein is likely less severe than those of variants that cause Swyer syndrome (described above). Individuals with 46,XY difference of sex development have a male-typical chromosome pattern (46,XY karyotype), but they  have external genitalia that do not look clearly male or clearly female or other abnormalities of the genitals and reproductive organs.  

Translocations that misplace the SRY gene onto an X chromosome cause about 10 percent of cases of a condition called ovotesticular difference of sex development. Individuals with this condition have a female-typical chromosome pattern (46,XX karyotype) and tissue from both female and male reproductive organs (ovarian and testicular tissue).