title: The role of SRY mutations in the etiology of gonadal dysgenesis in patients with 45,X/46,XY disorder of sex development and variants.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit of Developmental Endocrinology and Laboratory of Hormone and Molecular Genetics LIM/42, Hospital das Clinicas of the University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Mirian Yumie
authors.initials: MY
authors.lastname: Nishi
authors.forename: Elaine Maria Frade
authors.initials: EM
authors.lastname: Costa
authors.forename: Suely Beirão
authors.initials: SB
authors.lastname: Oliveira
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Sorahia
authors.initials: S
authors.lastname: Domenice
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006060:Gonadal Dysgenesis, Mixed / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D009030:Mosaicism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D051876:Sex-Determining Region Y Protein / Q000235:genetics*; D014424:Turner Syndrome / Q000209:etiology / Q000235:genetics
chemical_list: C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein