title: Normal female phenotype and ovarian development despite the ovarian expression of the sex-determining region of Y chromosome (SRY) in a 46,XX/69,XXY diploid/triploid mosaic child conceived after in vitro fertilization-intracytoplasmic sperm injection.
abstract: BACKGROUND
  Diploid/triploid mosaicism (mixoploidy) is a rare chromosomal abnormality characterized by mental and growth retardation, hypotonia, and dysmorphic features such as facial asymmetry, low-set ears, and syndactyly. All 46,XX/69,XXY cases fall into three phenotypic groups: male with testicular development, ovotestis disorder of sex development (DSD), or undervirilized male DSD. All phenotypic females with diploid/triploid mosaic reported so far had 46,XX/69,XXX karyotype.
  
  
  METHODS
  We report an 8-year-old girl conceived after in vitro fertilization-intracytoplasmic sperm injection with normal internal/external genital and ovarian development despite 46,XX/69,XXY mosaicism and normal expression of sex-determining region of Y chromosome (SRY) in her gonads.
  
  
  METHODS
  Because of the increased risk of gonadoblastoma resulting from Y chromosome mosaicism, her ovaries were removed by laparoscopy. Ovarian tissue was analyzed histologically as well as by fluorescence in situ hybridization, PCR, and RT-PCR amplification to determine the localization of Y chromosome and expression of SRY and DAX1 mRNA. Methylation-specific PCR was used to assess the inactivation pattern of X chromosomes.
  
  
  RESULTS
  By laparoscopy, internal female genital anatomy appeared to be normal. Cytogenetic and molecular methods confirmed the presence of intact and functionally active Y chromosome in the ovary. Strikingly, histological assessment of the gonads showed normal ovarian architecture with abundant primordial follicles despite the presence of the Y chromosome in ovarian follicles and the expression of SRY mRNA in gonadal tissue.
  
  
  CONCLUSIONS
  This case illustrates that normal ovarian development is possible in the presence of Y chromosome in ovarian follicles and despite the expression of SRY in ovarian tissue. Furthermore, this is the first documented case of mixoploidy after in vitro fertilization-intracytoplasmic sperm injection and the only phenotypic female with 46,XX/69,XXY karyotype.
authors.affiliation: Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, 505 East 70th Street, Suite HT300, New York, New York 10021, USA.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Oktem
authors.forename: Darius A
authors.initials: DA
authors.lastname: Paduch
authors.forename: Kangpu
authors.initials: K
authors.lastname: Xu
authors.forename: Anna
authors.initials: A
authors.lastname: Mielnik
authors.forename: Kutluk
authors.initials: K
authors.lastname: Oktay
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D019175:DNA Methylation; D002658:Developmental Disabilities / Q000235:genetics; D004171:Diploidy; D005260:Female; D006801:Humans; D008957:Models, Genetic; D009030:Mosaicism; D010053:Ovary / Q000254:growth & development* / Q000378:metabolism*; D010641:Phenotype; D025064:Sex Chromosome Disorders / Q000235:genetics*; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism*; D020554:Sperm Injections, Intracytoplasmic; D014314:Trisomy
chemical_list: D051876:Sex-Determining Region Y Protein