NR5A1

NR5A1 gene variants (also called mutations) have been identified in a small number of people 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.

Sex development usually follows a particular pattern based on an individual's chromosomes. People usually have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Girls and women typically have two X chromosomes (46,XX karyotype), while boys and men typically have one X chromosome and one Y chromosome (46,XY karyotype). However, individuals with Swyer syndrome have a male-typical chromosome pattern (46,XY karyotype), but they develop female-typical sex characteristics.

Variants in the NR5A1 gene in people with Swyer syndrome impair the function of steroidogenic factor 1. These changes affect the process of sex development, preventing affected individuals with a 46,XY karyotype from developing testes and causing them to develop female reproductive structures (a uterus and fallopian tubes).

MedlinePlus Genetics provides information about 46,XX testicular difference of sex development

NR5A1 gene variants have been identified in people with 46,XY disorder of sex development, also known as partial gonadal dysgenesis. Affected individuals may have external genitalia that do not look clearly male-typical or clearly female-typical or other abnormalities of the genitals and reproductive organs. Affected individuals may also have abnormalities of the adrenal glands, which may cause hormone deficiencies, resulting in a variety of health problems. NR5A1 gene variants that cause 46,XY disorder of sex development impair the function of steroidogenic factor 1, though likely to a lesser extent than variants that cause Swyer syndrome (described above).

NR5A1 gene variants that affect gonadal development and function have also been identified in people whose gonads do not produce reproductive cells (eggs or sperm). These conditions, which are called spermatogenic failure in men and primary ovarian insufficiency in women, result in an inability to conceive children (infertility).