Screening for Y-delived Sex Determining Gene SRY in Patients with Intersex

Objective: The gene SRY[sex determining region of the Y] located at the distal region of the short arm of the Y chromosome, is necessary for male sex determination in mammals. The mutation or translocation during meiotic division of SRY gene is suggested to be related with abnormal sexual differentiation. Also, the presence of Y chromosome in patients with gonadal dysgenesis is correlated with the risk of gonadoblastoma. Therefore, it is important to detect the presence of Y material in these patients. Also, SRY gene is reported to be expressed in many embryonic tissue and adult tissue[hidden mosaicism in the gonad], and the patients with abnormal sexual differentiation may have cryptic Y mosaicism. But sometimes it is difficult to detect Y material with karyotyping. This study was performed to evaluate the usefulness of the SRY gene screening by using PCR and FISH in detecting the presence of Y material and possible tissue mosaicism in patients with abnormal sexual differentiation. Methods: We screened for SRY gene by using PCR in peripheral leukocytes of 32 patients with abnormal sexual differentiation: twenty cases of Turner syndrome[7 45,XO, 2 46,Xi[Xq], 3 45,XO/46,XX, 5 45,XO/46,Xi[Xq], 1 45,XO/46,Xi[Yq], 1 46,XX[delXq24] and 1 46,X, mar], 4 cases of 46,XY pure gonadal dysgenesis, 5 46,XX true hermaphroditism, 1 46,XX sex reversal and 2 testicular feminization. In the gonadal tissue of 5 true hermaphroditism and 1 testicular feminization, we also performed FISH to detect SRY gene in gonad for detection of tissue mosaicism. Results: We were able to identify Y chromosome material in 2 of 20 Turner syndrome patients [45,XO/46,Xi[Xq], 45,XO/46,Xi[Yq]] and 3 from 4 46,XY pure gonadal dysgenesis, 2 testicular feminization, 1 46,XX sex reversal by using PCR technique with peripheral leukocytes. And SRY gene was identified in the gonadal tissue by using FISH in 1 of 5 patients with 46,XX true hermaphroditism, while SRY PCR was negative in peripheral leukocytes. SRY gene expression showed discrepancy between blood and gonadal tissue. In testicular feminization, both SRY PCR in blood and FISH in gonad were positive. Laparoscopic gonadectomy was performed in Turner syndrome, pure gonadal dysgenesis and testicular feminization containing Y chromosome or SRY gene. Conclusion: It is important to determine the presence of Y material in patients with abnormal sexual differentiation, even in the case of Y negative on karyotyping. because there may be tissue mosaicism of Y chromosome material in these patients. Therefore, it is necessary to evaluate Y material in various tissues in these patients and SRY gene screening by using PCR or FISH is sensitive and useful in detecting Y material and mosaicism among tissues.restrictio