Mutations in NR5A1 were first described in patients with primary adrenal insufficiency and 46,XY disorders of sexual development and later also in men with hypospadias, bilateral anorchia and micropenis and women with primary ovarian insufficiency.
A variant in steroidogenic factor-1 (SF-1, encoded by the gene NR5A1), p.Arg92Trp, has recently been reported in multiple families with 46,XX ovotesticular or testicular disorders of sex development (DSD).
NR5A1 mutations have been detected in 46,XY individuals with disorders of sexual development (DSD) but apparently normal adrenal function and in 46,XX women with normal sexual development yet primary ovarian insufficiency (POI).
The first human NR5A1 mutation was a heterozygous de novo p.G35E variant identified in a patient with disorder of sex development (DSD) 46,XY and primary adrenal insufficiency.
The steroidogenic factor-1 (SF-1, NR5A1) gene plays a key role in hypothalamic-pituitary-steroidogenic organ development, and has previously been reported to be mutated in individuals with 46,XY disorder of sex development.
NR5A1 is a key gene required for gonadal function, and variants are associated with a wide phenotypic spectrum of disorders of sexual development, and are found in 0.26-8% of patients with premature ovarian insufficiency.
Clinical applicability of rapid detection of SRY and DYS14 genes in patients with disorders of sex development using an indigenously developed 5' exonuclease based assay.
Unbalanced translocations of Y-chromosomal fragments harboring the sex-determining region Y gene (SRY) to the X chromosome or an autosome result in 46,XX and 45,X testicular disorders of sex development (DSD), respectively.
it was the aim of this study to screen for allelic variation in SRY in a large cohort of patients with disorders of sex development due to chromosomal abnormalities with 45,X/46,X,der(Y) karyotype.
A disorder of sex development (DSD) in dogs with female sex chromosomes (78, XX), a lack of the SRY gene and the presence of testes or ovotestes is commonly diagnosed in numerous breeds.
We aimed to identify the genetic cause in a cohort of 11 unrelated cases and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD).
Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition) with dysgenic gonads.
However, testicular tissue does develop in the absence of SRY, albeit rarely, which is the case in testicular XX (SRY-negative) disorder of sex development (DSD).
Multiple cases of Disorders of Sex Development in human patients or sex reversal in mice and other vertebrates can be explained by mutations affecting upstream regulators of Sox9 expression, such as the product of the Y chromosome gene Sry that triggers testis differentiation.
Association between polymorphisms in the SOX9 region and canine disorder of sex development (78,XX; SRY-negative) revisited in a multibreed case-control study.
Through copy number variation mapping this study identified duplications upstream of the SOX9 gene in three families with an isolated 46,XX disorder of sex development (DSD) and an overlapping deletion in one family with two probands with an isolated 46,XY DSD.