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SignatureChip® Detection Rates and Fact Sheet for SRY Dosage Abnormalities

The sex determining region (SRY) gene is located on Yp11.31. Dosage abnormalities of SRY (i.e. loss of SRY on the Y chromosome or presence of SRY on other chromosomes) are responsible for disorders of sexual differentiation., such as XX male syndrome and XY gonadal dysgenesis.

XX male syndrome: XX karyotype with male phenotype (external genitalia normal to ambiguous, normal testicles, azoospermia, lacking internal female structures).

80% of XX males have SRY. Typically, XX males with SRY have normal external genitalia and develop gynecomastia around the time of puberty. Presence of SRY on an X chromosome is typically due to interchange between pseudoautosomal regions on the X and Y p-arms.

20% of XX males have no SRY. Typically, XX males with no SRY have some level of genital ambiguity and are more likely to have gynecomastia prior to puberty. The cause of masculinization in these individuals is not well understood. Explanations for some cases may include: low level XX/XY or XX/XXY mosaicism which is known to cause overlapping features, SOX9 duplication on chromosome 17q (one case has been reported; Medline), or autosomal recessive inheritance (one large family has been reported; Medline).

XY females: XY karyotype with female phenotype (range of normal primary and secondary sexual characteristics, defined by individual syndrome).

Loss of SRY on the Y chromosome causes XY gonadal dysgenesis, also called Swyer syndrome, causing failure of pubertal development, lack of external secondary sexual characteristics, and streak gonads internally with an increased risk for gonadoblastoma.  Expressivity in families is variable.

10-15% of females with XY gonadal dysgenesis have a deletion of SRY, while an additional 10-15% have an SRY point mutation.  Females with XY gonadal dysgenesis and no SRY abnormalities may have mutations in other genes, such as deletion of the DMRT1 and/or DMRT2 genes on chromosome 9p which has been rarely reported (Medline), but other etiologies are not well known.

XY females with other phenotypes include Androgen insensitivity syndrome (AIS), caused by mutations in the androgen receptor gene, as well as disorders causing extragonadal defects in addition to the female phenotype, such as Campomelic dysplasia.