Abstract
BackgroundThe presence of the Y-chromosome or Y chromosome-derived material is seen in 4-60% of Turner syndrome patients (Chromosomal Disorders of Sex Development (DSD)). DSD patients with specific Y-chromosomal material in their karyotype, the GonadoBlastoma on the Y-chromosome (GBY) region, have an increased risk of developing type II germ cell tumors/cancer (GCC), most likely related to TSPY. The Sex determining Region on the Y gene (SRY) is located on the short arm of the Y-chromosome and is the crucial switch that initiates testis determination and subsequent male development. Mutations in this gene are responsible for sex reversal in approximately 10-15% of 46,XY pure gonadal dysgenesis (46,XY DSD) cases. The majority of the mutations described are located in the central HMG domain, which is involved in the binding and bending of the DNA and harbors two nuclear localization signals. SRY mutations have also been found in a small number of patients with a 45,X/46,XY karyotype and might play a role in the maldevelopment of the gonads.MethodsTo thoroughly investigate the presence of possible SRY gene mutations in mosaic DSD patients, we performed next generation (deep) sequencing on the genomic DNA of fourteen independent patients (twelve 45,X/46,XY, one 45,X/46,XX/46,XY, and one 46,XX/46,XY).Results and conclusionsThe results demonstrate that aberrations in SRY are rare in mosaic DSD patients and therefore do not play a significant role in the etiology of the disease.
Highlights
The presence of the Y-chromosome or Y chromosome-derived material is seen in 4-60% of Turner syndrome patients (Chromosomal Disorders of Sex Development (DSD))
Patients with chromosomal DSD as a result of a 45,X/46,XY karyotype may present with a wide spectrum of phenotypes ranging from normal male through ambiguous genitalia to female with a Turner syndrome (TS) phenotype [5]
In total fourteen chromosomal DSD patients with a mosaic karyotype were included in the study: twelve patients with a 45,X/46,XY, one patient with a 45,X/46, XX/46,XY, and one patient with a 46,XY/46,XX sex chromosomal DSD (Table 1)
Summary
The presence of the Y-chromosome or Y chromosome-derived material is seen in 4-60% of Turner syndrome patients (Chromosomal Disorders of Sex Development (DSD)). The Sex determining Region on the Y gene (SRY) is located on the short arm of the Y-chromosome and is the crucial switch that initiates testis determination and subsequent male development Mutations in this gene are responsible for sex reversal in approximately 10-15% of 46,XY pure gonadal dysgenesis (46,XY DSD) cases. Patients with chromosomal DSD as a result of a 45,X/46,XY karyotype (mixed gonadal dysgenesis) may present with a wide spectrum of phenotypes ranging from normal male through ambiguous genitalia to female with a TS phenotype [5] They are characterized by the presence of dysgenetic testis and/or streak gonads, with persistence of the Müllerian ducts and inadequate virilization, and classically have a 45,X/46,XY karyotype. The presence of a specific region of the Y-chromosome in TS patients is correlated with an increased risk of developing a GCC, namely the GonadoBlastoma on Y region (GBY, i.e. TSPY) [8,9]
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