Test ID: FSRY    
Sex-Determining Region Y, Yp11.3 Deletion, FISH

Aiding in the detection of the SRY gene in males with primary infertility, XY females, and individuals with ambiguous genitalia, in conjunction with conventional chromosome studies (CMS/8696 Chromosome Analysis, for Congenital Disorders, Blood)

Appropriate to aid in detecting the presence or absence of the SRY gene in XX males, XY females, and infertile XY males. Must be ordered in conjunction with conventional chromosome studies (#8696 Chromosome Analysis, For Congenital Disorders, Blood).

The SRY (sex-determining region on the Y chromosome) gene is required for normal embryonic wolffian (male) genital development, although numerous other genes are involved in completing the process of normal male development. Some gene mutations block the action of SRY in development. Thus, a 46,XY individual with an SRY deletion or mutation will develop as a female, and a 46,XX individual with translocation of SRY to 1 X chromosome will develop as a male. Structural abnormalities of the Y chromosome result in a spectrum of abnormalities from primary infertility (male or female) to various forms of ambiguous genitalia. SRY-negative 46,XX males often have ambiguous genitalia, whereas those who are positive for SRY usually have a normal male phenotype with azoospermia. SRY-negative 46,XY females may have another mutation, such as 1 involving the SOX9 gene.

We recommend conventional chromosome studies (CMS/8696 Chromosome Analysis, for Congenital Disorders, Blood) to detect Y chromosome abnormalities and to rule out other chromosome abnormalities or translocations, and FISH studies to detect cryptic translocations involving the SRY region that are not demonstrated by conventional chromosome studies.

An interpretive report will be provided.

Any male individual with an SRY signal on a structurally normal Y chromosome is considered negative for a deletion in the region tested by this probe. Any patient with a FISH signal pattern indicating loss of the critical region will be reported as having a deletion of the regions tested by this probe. Any patient with a FISH signal on an X chromosome will be reported as having a cryptic X;Y translocation involving the critical region.

This FISH test is not approved by the FDA.

Using a probe for the SRY critical region, FISH analysis was performed on a series of 46 patient specimens, peripheral blood or amniotic fluid, and results were compared to cytogenetic analyses and the patient's phenotype.

Of 20 phenotypic females:

-12 with a 45,X karyotype or an X duplication exhibited no SRY signal

-8 with a 46,XY karyotype or an abnormal Y were SRY positive

Of 20 phenotypic males:

-7 of 8 with a 46,XX karyotype were SRY negative

-13 with a 46, XY with a normal or rearranged Y chromosome were SRY positive

Of 25 controls:

-13 males exhibited SRY on the Y chromosome

-12 females exhibited no SRY signal

1. Margarit E, Coll MD, Oliva R, et al: SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite. Am J Med Genet 2000 Jan;90(1):25-28

2. Lopez M, Torres L, Mendez JP, et al: SRY alone can induce normal male sexual differentiation. Am J Med Genet 1995 Jan;55(3):356-358

• Final Disposition of Fetal/Stillborn Remains
• Informed Consent for Genetic Testing