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SRY mutation analysis by next generation (deep) sequencing in a cohort of chromosomal Disorders of Sex Development (DSD) patients with a mosaic karyotype

Remko Hersmus1, Hans Stoop1, Erin Turbitt4, J Wolter Oosterhuis1, Stenvert LS Drop3, Andrew H Sinclair4, Stefan J White2 and Leendert HJ Looijenga1*

Author Affiliations

1 Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

2 Centre for Reproduction and Development, Monash Institute of Medical Research, Clayton, Victoria, Australia

3 Department of Pediatric Endocrinology, Erasmus MC - University Medical Center Rotterdam, Sophia Children’s Hospital, Rotterdam, The Netherlands

4 Murdoch Children’s Research Institute, and Department of Pediatrics, University of Melbourne, Royal Children’s Hospital, Melbourne, Victoria, Australia

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BMC Medical Genetics 2012, 13:108  doi:10.1186/1471-2350-13-108

Published: 16 November 2012



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)). 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.


To 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 conclusions

The 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.

Disorders of Sex Development (DSD); Chromosomal-DSD; SRY; Next generation (deep) sequencing; Mutation