title: A novel SRY mutation leads to asymmetric SOX9 activation and is responsible for mixed 46,XY gonadal dysgenesis.
abstract: BACKGROUND
  SRY, located on the Y chromosome, is one of the key genes involved in human sex determination. SRY mutations are responsible for 10-15% of all cases of 46,XY gonadal dysgenesis (GD) but are rarely implicated in the pathogenesis of mixed GD.
  
  
  METHODS
  SRY was analyzed by sequence analysis of DNA extracted from blood leukocytes. SRY activity was evaluated by SOX9 immunostaining, one of the targets of SRY.
  
  
  RESULTS
  We report a case of mixed GD due to a novel SRY point mutation in a patient with a 46,XY karyotype, without mosaicism or submicroscopic genomic imbalances. Hormonal studies showed low anti-müllerian hormone and histological examination of the gonads showed a streak gonad on the right side and a left dysgenetic testis, thus permitting the diagnosis of mixed GD. Immunostaining for SOX9, a target of SRY, was positive in nuclei of Sertoli and epididymal cells in the left gonad and negative on the right, thus indicating asymmetric activation of SRY.
  
  
  CONCLUSIONS
  Mixed GD can result from SRY mutations without mosaicism, neither in peripheral blood, nor within the gonads. The asymmetric effect of the point mutation implies the presence of local factors modulating SRY expression or action.
authors.affiliation: Endocrine and Diabetes Unit, Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland. philippe.klee@hcuge.ch
authors.forename: Philippe
authors.initials: P
authors.lastname: Klee
authors.forename: Frédérique
authors.initials: F
authors.lastname: Béna
authors.forename: Jacques
authors.initials: J
authors.lastname: Birraux
authors.forename: Sophie
authors.initials: S
authors.lastname: Dahoun
authors.forename: Mirjam
authors.initials: M
authors.lastname: Dirlewanger
authors.forename: Céline
authors.initials: C
authors.lastname: Girardin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Plotton
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Rougemont
authors.forename: Yves
authors.initials: Y
authors.lastname: Morel
authors.forename: Valérie M
authors.initials: VM
authors.lastname: Schwitzgebel
mesh_terms: D002675:Child, Preschool; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009030:Mosaicism; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein