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.