The role of SRY mutations in the etiology of gonadal dysgenesis in patients with 45,X/46,XY disorder of sex development and variants.

Background: The potential involvement of SRY in abnormal gonadal development in 45,X/46,X,der(Y) patients was proposed following the identification of SRY mutations in a few patients with Turner syndrome (TS). However, its exact etiological role in gonadal dysgenesis in patients with Y chromosome mosaicisms has not yet been clarified.

Aims: it was the aim of this study to screen for allelic variation in SRY in a large cohort of patients with disorders of sex development due to chromosomal abnormalities with 45,X/46,X,der(Y) karyotype.

Patients: twenty-seven patients, 14 with TS and 13 with mixed gonadal dysgenesis (MGD), harboring 45,X/46,X,der(Y) karyotypes were selected.

Methods: Genomic DNA was extracted from peripheral blood leukocytes of all patients and from gonadal tissue in 4 cases. The SRY coding region was PCR amplified and sequenced.

Results: We identified only 1 polymorphism (c.561C→T) in a 45,X/46,XY MGD patient, which was detected in blood and in gonadal tissue.

Conclusion: our results indicate that mutations in SRY are rare findings in patients with Y chromosome mosaicisms. Therefore, a significant role of mutated SRY in the etiology of gonadal dysgenesis in patients harboring 45,X/46,XY karyotype and variants seems very unlikely.