The existence of an X-specific gene involved in human sex determination was first postulated by German et al. (1978), on the basis of a family with an apparent X-linked mode of inheritance of 46,XY gonadal dysgenesis. A number ... The existence of an X-specific gene involved in human sex determination was first postulated by German et al. (1978), on the basis of a family with an apparent X-linked mode of inheritance of 46,XY gonadal dysgenesis. A number of families with X-linked recessive (or sex-limited autosomal dominant) transmission of the disorder were reported thereafter (reviewed by Fechner et al., 1993). Bardoni et al. (1994) provided a review of 12 individuals with partial duplications of Xp and an intact SRY gene described in the literature. Of these 12, 8 had female or ambiguous external genitalia, and in 2 cases histologic examination of the gonads demonstrated impaired testis formation. Smyk et al. (2007) reported a 21-year-old 46,XY female who presented with primary amenorrhea, a small immature uterus, and gonadal dysgenesis without adrenal insufficiency, in whom they identified a submicroscopic 257-kb deletion with a distal breakpoint 11.3 kb upstream of the NR0B1 gene. The deletion was also present in the patient's mother, who had a history of ovarian cysts, but was not found in 1,184 controls. The authors suggested that loss of regulatory sequences may have resulted in position effect upregulation of NR0B1 expression.
Bardoni et al. (1994) identified a locus on the X chromosome which, when present in duplicate, resulted in male-to-female sex reversal. Alterations at this locus, in a 160-kb region of Xp21 adjacent to the congenital adrenal hypoplasia locus ... Bardoni et al. (1994) identified a locus on the X chromosome which, when present in duplicate, resulted in male-to-female sex reversal. Alterations at this locus, in a 160-kb region of Xp21 adjacent to the congenital adrenal hypoplasia locus (see 300200), constitute one of the causes of sex reversal in individuals with a normal 46,XY karyotype. Identification of males deleted for DSS suggested that the locus is not required for testis differentiation. Bardoni et al. (1994) proposed that DSS has a role in ovarian development and/or functions as a link between ovary and testis formation.