title: SRY mutation analysis by next generation (deep) sequencing in a cohort of chromosomal Disorders of Sex Development (DSD) patients with a mosaic karyotype.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  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.
authors.affiliation: Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: Remko
authors.initials: R
authors.lastname: Hersmus
authors.forename: Hans
authors.initials: H
authors.lastname: Stoop
authors.forename: Erin
authors.initials: E
authors.lastname: Turbitt
authors.forename: J Wolter
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: Stenvert Ls
authors.initials: SL
authors.lastname: Drop
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Sinclair
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: White
authors.forename: Leendert Hj
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D041322:Chromosomes, Human, Y / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D018238:Gonadoblastoma / Q000235:genetics; D006801:Humans; D007223:Infant; D059785:Karyotype; D008297:Male; D009030:Mosaicism; D012732:Sex Determination Analysis; D051876:Sex-Determining Region Y Protein / Q000235:genetics* / Q000378:metabolism; D046468:Sexual Development / Q000235:genetics; D013737:Testis / Q000002:abnormalities*; D014157:Transcription Factors / Q000235:genetics; D014424:Turner Syndrome / Q000235:genetics*
chemical_list: C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors