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

J Clin Endocrinol Metab. 2007 Mar;92(3):1008-14. doi: 10.1210/jc.2006-1963. Epub 2006 Dec 12.

Abstract

Context: 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.

Patient: 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.

Intervention: 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.

Conclusion: 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.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Chromosome Aberrations
  • Chromosome Banding
  • DNA Methylation
  • Developmental Disabilities / genetics
  • Diploidy*
  • Female
  • Humans
  • Models, Genetic
  • Mosaicism*
  • Ovary / growth & development*
  • Ovary / metabolism*
  • Phenotype
  • Sex Chromosome Disorders / genetics*
  • Sex-Determining Region Y Protein / genetics
  • Sex-Determining Region Y Protein / metabolism*
  • Sperm Injections, Intracytoplasmic*
  • Trisomy*

Substances

  • Sex-Determining Region Y Protein