Heterozygous mutations of NR5A1, which encodes steroidogenic factor 1 (SF1), were identified in patients with 46,XY disorders of sex development (DSD) with normal adrenal function.
Heterozygous SF1 loss-of-function mutations in these cases resulted in mild DSD manifestations, such as dysgenetic testes, spontaneous puberty, and preserved adrenal function.
As NR5A1 mutations can cause a wide spectrum of DSD with relatively high frequency, the analysis of the NR5A1 gene by MLPA is quite important and should be extended to larger groups of patients.
Among the remaining 70 cases there were patients with chromosome abnormalities which are not included in the DSD classification as well as rare NR5A1 variants of uncertain significance and hypergonadotropic hypogonadism and microorchidism in 46,XY subjects.
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).
A novel heterozygous mutation of steroidogenic factor-1 (SF-1/Ad4BP) gene (NR5A1) in a 46, XY disorders of sex development (DSD) patient without adrenal failure.
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).