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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

Center for Reproductive Medicine and Infertility (O.O., D.A.P., K.X., K.O.) and the Department of Urology (D.A.P.), Weill Medical College of Cornell University, New York, New York 10021; and The Population Council, Center for Biomedical Research (D.A.P., A.M.), New York, New York 10021

Address all correspondence and requests for reprints to: Dr. Kutluk Oktay, Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, 505 East 70th Street, Suite HT300, New York, New York 10021. E-mail: koktay{at}fertilitypreservation.org.

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.